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Placental Gas Exchange and the Oxygen Supply to the Fetus

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ABSTRACT

The oxygen supply of the fetus depends on the blood oxygen content and flow rate in the uterine and umbilical arteries and the diffusing capacity of the placenta. Oxygen consumption by the placenta is a significant factor and a potential limitation on availability to the fetus. The relevance of these several factors as well as responses to acute or sustained hypoxia has been explored in the sheep model. In addition, much has been learned in the context of hypobaric hypoxia by studying human populations that have resided at high altitude for varying periods of time. Embryonic development occurs under anaerobic conditions and even the fetus is adapted to a low oxygen environment. Nevertheless, there is a reserve capacity, and during acute hypoxia the fetus can counter a 50% reduction in oxygen delivery by increasing fractional extraction. During sustained hypoxia, on the other hand, fetal growth is slowed, although oxygen consumption is unaltered when corrected for fetal mass. Similarly, birth weight is reduced in humans living at high altitude even if the effect is tempered in those with a long highland ancestry. Placental mass changes little during sustained hypoxia in sheep or humans at high altitude. This conceals the fact that there are structural changes and that placental oxygen consumption is reduced. The underlying mechanisms are a current focus of research. One intriguing possibility is that increased anaerobic metabolism of glucose in the placenta spares oxygen for the fetus but reduces its supply of substrate and thereby limits fetal growth. © 2015 American Physiological Society. Compr Physiol 5:1381‐1403, 2015.

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Figure 1. Figure 1. Effect on fetal oxygen consumption (upper panel) and oxygen extraction (lower panel) of reducing umbilical blood flow in the fetal lamb by partial cord occlusion. Error bars are SD. Reproduced, with permission, from (); Copyright © 1983 with permission from Elsevier.
Figure 2. Figure 2. Oxygen binding to human embryonic hemoglobins. The saturation of hemoglobin with oxygen as a function of PO2 is shown for adult hemoglobin (black circles) and embryonic hemoglobins Gower I (black inverted triangles), Portland (open circles), and Gower II (open squares). Reproduced, with permission, from (); Copyright © 2002 with permission from Elsevier.
Figure 3. Figure 3. Blood oxygen content as a function of PO2 for human maternal and near term fetal blood. A and V, maternal arterial and venous values; a and v, umbilical arterial and venous values. Reproduced, with permission, from (); Copyright © 1987 The American Physiological Society.
Figure 4. Figure 4. Effect on fetal oxygen delivery (DO2 fetus), oxygen extraction and oxygen uptake (VO2 fetus) of varying the hematocrit of the fetal lamb by exchange transfusion. Reproduced from (); Copyright © 1985 with permission from Elsevier.
Figure 5. Figure 5. The interhemal barrier of the human placenta. The intervillous space is separated from blood in the fetal capillary by syncytiotrophoblast and fetal capillary endothelium with their basal membranes. A very thin layer of connective tissue cytoplasm is interposed between the two basal membranes. Courtesy of Dr. Allen C. Enders.
Figure 6. Figure 6. Effects of acute and chronic hypoxemia on fetal and placental oxygen uptake in the sheep. (A) Effect of an acute 60‐min reduction in uterine blood flow on oxygen uptake of the fetus and placenta. Placental oxygen consumption is maintained at the expense of the fetus. Data adapted, from (). (B) Effect of long‐term restriction in uterine oxygen and substrate supply (following carunclectomy) on oxygen uptake of the fetus and placenta. Placental oxygen consumption is reduced to a greater extent than that of the fetus. Data adapted, from (). Error bars are SEM. Reproduced, with permssion, from (); Copyright © 2000 with permission from Elsevier.
Figure 7. Figure 7. Principal pathways of the fetal circulation and representative values for oxygen saturation of the blood. Well oxygenated blood from the umbilical vein (UV) is directed through the ductus venosus (DV) (or left lobe of the liver) across the inferior vena cava (IVC), through the foramen ovale (FO), left atrium (LA), and ventricle and up the ascending aorta (AO) toward the common carotid arteries (CCA). Deoxygenated blood from the superior vena cava (SVC) and IVC passes through the right atrium (RA), right ventricle, pulmonary artery (PA), and ductus arteriosus (DA). FOV, foramen ovale valve; LHV, left hepatic vein; MHV, medial hepatic vein; PV, pulmonary vein; RHV, right hepatic vein. Reproduced, with permission, from (); Copyright © 2004 John Wiley & Sons, Ltd.
Figure 8. Figure 8. Uterine artery blood flow at low and high altitude in women of European and Andean descent. (A) At low altitude, the pregnancy‐associated rise in uterine blood flow was similar in Andean and European women. (B) At high altitude, the pregnancy‐associated rise in uterine blood flow was greater in Andeans than in Europeans, resulting in blood flows that were more than one‐third larger at 20 or 38 weeks in Andean women. Error bars are SEM. Asterisks, P < 0.05. Reproduced, with permission, from (); Copyright © 2009 The American Physiological Society.
Figure 9. Figure 9. Plasma glucose concentrations in umbilical vessels and fetal glucose uptake in term human pregnancies at low (400 m) and high (3600 m) altitude. (A) Umbilical arterial and venous plasma glucose concentrations were lower at high than at low altitude. (B) The fetal venous‐to‐arterial plasma glucose concentration difference (ΔFV‐FA) was similar at low and high altitude. (C) Fetal glucose consumption (corrected for birth weight) was greater at low than at high altitude. Error bars are SEM. Reproduced, with permission, from (); Copyright © 2010 Zamudio et al.
Figure 10. Figure 10. Blood oxygen dissociation curves of maternal and fetal blood of llamas (upper panel) and sheep (lower panel). Maternal blood has a relatively high oxygen affinity in the llama. Reproduced, with permission, from (); Copyright © 1996 with permission from Elsevier.
Figure 11. Figure 11. Fetal oxygen consumption (upper panel) and arterial blood base excess (lower panel) as a function of fetal oxygen delivery in sheep. Fetal oxygen uptake remained constant until oxygen delivery was reduced below ca. 13 mL min−1 kg−1 fetal mass (0.6 mmol min−1 kg−1). There was then an increase in anaerobic metabolism with a resultant fall in arterial base excess. Data are from experiments in which both oxygen affinity (hemoglobin type) and oxygen capacity (hemoglobin concentration) were varied. Circles: fetal hemoglobin; squares: adult hemoglobin; filled circles and squares: normal hematocrit; half‐filled circles and squares: moderate anemia; open circles and squares: severe anemia. Reproduced, with permission, from (); Copyright © 1989 with permission from Elsevier.


Figure 1. Effect on fetal oxygen consumption (upper panel) and oxygen extraction (lower panel) of reducing umbilical blood flow in the fetal lamb by partial cord occlusion. Error bars are SD. Reproduced, with permission, from (); Copyright © 1983 with permission from Elsevier.


Figure 2. Oxygen binding to human embryonic hemoglobins. The saturation of hemoglobin with oxygen as a function of PO2 is shown for adult hemoglobin (black circles) and embryonic hemoglobins Gower I (black inverted triangles), Portland (open circles), and Gower II (open squares). Reproduced, with permission, from (); Copyright © 2002 with permission from Elsevier.


Figure 3. Blood oxygen content as a function of PO2 for human maternal and near term fetal blood. A and V, maternal arterial and venous values; a and v, umbilical arterial and venous values. Reproduced, with permission, from (); Copyright © 1987 The American Physiological Society.


Figure 4. Effect on fetal oxygen delivery (DO2 fetus), oxygen extraction and oxygen uptake (VO2 fetus) of varying the hematocrit of the fetal lamb by exchange transfusion. Reproduced from (); Copyright © 1985 with permission from Elsevier.


Figure 5. The interhemal barrier of the human placenta. The intervillous space is separated from blood in the fetal capillary by syncytiotrophoblast and fetal capillary endothelium with their basal membranes. A very thin layer of connective tissue cytoplasm is interposed between the two basal membranes. Courtesy of Dr. Allen C. Enders.


Figure 6. Effects of acute and chronic hypoxemia on fetal and placental oxygen uptake in the sheep. (A) Effect of an acute 60‐min reduction in uterine blood flow on oxygen uptake of the fetus and placenta. Placental oxygen consumption is maintained at the expense of the fetus. Data adapted, from (). (B) Effect of long‐term restriction in uterine oxygen and substrate supply (following carunclectomy) on oxygen uptake of the fetus and placenta. Placental oxygen consumption is reduced to a greater extent than that of the fetus. Data adapted, from (). Error bars are SEM. Reproduced, with permssion, from (); Copyright © 2000 with permission from Elsevier.


Figure 7. Principal pathways of the fetal circulation and representative values for oxygen saturation of the blood. Well oxygenated blood from the umbilical vein (UV) is directed through the ductus venosus (DV) (or left lobe of the liver) across the inferior vena cava (IVC), through the foramen ovale (FO), left atrium (LA), and ventricle and up the ascending aorta (AO) toward the common carotid arteries (CCA). Deoxygenated blood from the superior vena cava (SVC) and IVC passes through the right atrium (RA), right ventricle, pulmonary artery (PA), and ductus arteriosus (DA). FOV, foramen ovale valve; LHV, left hepatic vein; MHV, medial hepatic vein; PV, pulmonary vein; RHV, right hepatic vein. Reproduced, with permission, from (); Copyright © 2004 John Wiley & Sons, Ltd.


Figure 8. Uterine artery blood flow at low and high altitude in women of European and Andean descent. (A) At low altitude, the pregnancy‐associated rise in uterine blood flow was similar in Andean and European women. (B) At high altitude, the pregnancy‐associated rise in uterine blood flow was greater in Andeans than in Europeans, resulting in blood flows that were more than one‐third larger at 20 or 38 weeks in Andean women. Error bars are SEM. Asterisks, P < 0.05. Reproduced, with permission, from (); Copyright © 2009 The American Physiological Society.


Figure 9. Plasma glucose concentrations in umbilical vessels and fetal glucose uptake in term human pregnancies at low (400 m) and high (3600 m) altitude. (A) Umbilical arterial and venous plasma glucose concentrations were lower at high than at low altitude. (B) The fetal venous‐to‐arterial plasma glucose concentration difference (ΔFV‐FA) was similar at low and high altitude. (C) Fetal glucose consumption (corrected for birth weight) was greater at low than at high altitude. Error bars are SEM. Reproduced, with permission, from (); Copyright © 2010 Zamudio et al.


Figure 10. Blood oxygen dissociation curves of maternal and fetal blood of llamas (upper panel) and sheep (lower panel). Maternal blood has a relatively high oxygen affinity in the llama. Reproduced, with permission, from (); Copyright © 1996 with permission from Elsevier.


Figure 11. Fetal oxygen consumption (upper panel) and arterial blood base excess (lower panel) as a function of fetal oxygen delivery in sheep. Fetal oxygen uptake remained constant until oxygen delivery was reduced below ca. 13 mL min−1 kg−1 fetal mass (0.6 mmol min−1 kg−1). There was then an increase in anaerobic metabolism with a resultant fall in arterial base excess. Data are from experiments in which both oxygen affinity (hemoglobin type) and oxygen capacity (hemoglobin concentration) were varied. Circles: fetal hemoglobin; squares: adult hemoglobin; filled circles and squares: normal hematocrit; half‐filled circles and squares: moderate anemia; open circles and squares: severe anemia. Reproduced, with permission, from (); Copyright © 1989 with permission from Elsevier.
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Anthony M. Carter. Placental Gas Exchange and the Oxygen Supply to the Fetus. Compr Physiol 2015, 5: 1381-1403. doi: 10.1002/cphy.c140073