FETAL CIRCULATION

IN HEALTH AND DISEASE

Flow Chart of Fetal Circulation

Characteristics of fetal circulatory dynamics

Parallel arrangement of two main arterial systems and their respective ventricles. Mixing of venous return and preferential streaming. High impedance and low flow of pulmonary circulation. Low impedance and high flow of placental circulation. Presence of shunts.

Cardiac output and its distribution Fetal lamb

CVO is 450 ml/kg/wt RV ejects 2/3 and LV ejects 1/3 of CVO UV flow is 200 ml/mt/kg [45% of CVO] Of this,110 ml/mt [24%] passes through DV and 90 ml/mt[21%] passes through hepatic circulation

Cardiac output and its distribution Fetal lamb

Portal venous flow forms 7% and of CVO and abdominal IVC blood forms 30% of CVO. Total venous return to heart from IVC is 315 ml/mt and represents 70% of CVO. Of this 115 ml/mt [25% of CVO] passes through FO and and 200 ml/mt [44%] passes through TV.

Cardiac output and its distribution Fetal lamb

Venous return to heart from SVC is 90 ml/mt/ and represents 21% of CVO most of this passes through tricuspid valve. RV ejects about 300 ml/mt or about 66% of CVO. About 35 ml/mt [8% of CVO] enters the pulmonary circulation

Cardiac output and its distribution Fetal lamb

About 265 ml/mt [60%]passes through ductus arteriosus. LV ejects 150 ml/kg [ 33% ]. Of this,90 ml/mt [20%] distributed to head and upper half and 45 ml/mt [10%]passes through isthmus. 3% of CVO enters coronary circulation.

60% AA 33% 21% 18

20%

28 19

8%

66% 70% 24% 21% 32

24

70%

45%

55%

65%

50%

65% 55%

35%

Cardiac output and its distribution human fetus

Limited data only is available based on doppler studies. Umbilical blood flow is 180 ml/mt /kg of estimated fetal weight. Pulmonary blood flow is estimated to be 75 ml/kg of fetal weight

Cardiac output and its distribution human fetus

CVO appears to be similar to that in lamb, 450 ml/mt/kg fetal weight Ratio of RV output to LV output is only 1.2 to 1.3 as compared to 2:1 in fetal lamb

140

45 175

15 250 200 220 95 140 15 220 40 125

75

75 180

31

10 39

3
58 44 49 31 21 28 17 3

17

49
39 10

Venous return to heart

Umbilical vein gives branches to left lobe of liver and then divides into DV and arcuate vien. Arcuate vien joins the portal vein and then gives of branches to right lobe of liver. Left hepatic vein joins the DV at its entry to IVC and Right hepatic vein joins the IVC directly.

Venous return to heart

Right lobe of liver poorly oxygenated portal venous blood and left lobe receives well oxygenated umbilical venous blood. Both lobes receive small contribution of blood from hepatic artery. Saturation of RHV is lower than that of LHV.

Venous return to heart

Posterior and left stream of IVC blood carries oxygenated blood while anterior and right stream carries poorly oxygenated blood. Preferential streaming of DV and LHV blood across the foramen ovale and abdominal IVC and RHV blood across the TV.

Venous return to heart

Eustechian valve helps to direct the IVC blood to cross the foramen ovale. The lower margin of septum secundum [christa dividens] helps to direct the left posterior stream to preferentially across the foramen ovale. SVC blood is directed aross the TV.

Shunts in fetal circulation

Ductus venosus Foramen ovale Ductus arteriosus or aortic isthmus

Shunts in fetal circulation

The blood returning to heart through venacavae and then redistributed to tissues without being delivered to placenta represents effective R to L shunt. The blood which passes through DV and then reaches DA and goes to placenta without getting distributed to tissues represent effective L to R shunt. Combined R to L and L to R shunts forms 33% of CVO.

PULMONARY CIRCULATION
Fetal lung does not serve gas exchange function. PVR is high and PBF is low. This helps to reduce workload of fetal heart.

PULMONARY CIRCULATION
MPA continues as Ductus and RPA and LPA arise as branches. Medial layer is composed of smooth muscle predominantly in small pre acinar and large acinar level arteries. Further branches have no muscular component.

PULMONARY CIRCULATION
PA pressure rises gradually paralleling the rise in aortic pressure. TPR falls gradually but this fall when correlated with rise in lung weight, there is actually an increase in PVR towards term . PBF increases gradually.

PULMONARY CIRCULATION
MPA has forward flow throughout systole with a short period of backflow at end of systole. DA also has forward flow throughout systole. BPA has forward flow only through initial one third of systole followed by back flow through rest of systole and diastole. In humans forward flow is more prolonged.

PULMONARY CIRCULATION
Experiments show fetal PBF increases dramatically in response to increase in maternal PO2. This response is evident only in latter part of gestation. Doppler studies indicate similar changes in humans as well.

PULMONARY CIRCULATION
Fetal pulmonary endothelium behaves in a similar fashion as adult endothelium to vasodilators. Adrenomedullin has a potent and prolonged vasodilatory effect. Leukotriens may be responsible for maintaining high fetal PVR.

PULMONARY CIRCULATION
Breathing at birth is associated with a marked fall in PVR and rise in PBF. PA pressure does not fall as rapidly and remain elevated till the Ductus is widely patent. Once the ductus is closed, PA pressure can vary independent of systemic pressure.

Oxygen exchange function

Higher hemoglobin level in fetus as compared to mother facilitates oxygen uptake by the fetus in the placenta. Oxygen dissociation curve of fetal red cells is shifted to left as compared to adult red cells. HbF has less affinity towards organic phosphates like 2,3 DPG and ATP.

Oxygen exchange function

These phosphates that are present in red cells compete with oxygen for binding to hemoglobin. Affinity of reduced hemoglobin to 2,3 DPG is higher than that of oxyhemoglobin and this facilitates oxygen delivery at tissue site. This is not significant in fetal hemoglobin.

Oxygen exchange function

As CO2 crosses placenta from fetus to mother,it creates a local acidosis. In the face of decreasing Ph,mothers hemoglobin shows less affinity towards Hb and oxygen release is enhanced.[Bohr effect] This supports diffusion of more oxygen across the diffusion membrane to fetus.

Oxygen exchange function

As O2 is released,maternal Hb acts as a buffer that removes H+ from local environment. This encourages production of bicarbonate from H2O and CO2 thereby reducing local PC02 and facilitating diffusion of CO2 from fetus.

Post natal changes

Gas exchange function is transferred from placenta to the lungs. Separation of systemic and pulmonary circulations Increased metabolism to maintain body temperature and hence increased cardiac output.

FETAL CIRCULATION VIII: Conversion to post-natal*

Closure of Foramen ovale Forces venous blood (now all deoxygenated) into the right ventricle for expulsion to the lungs Closure of DUCTUS VENOSUS Stops use of umbilical vessels, & converts all vena cava blood to deoxygenated HEART Vena cava Right IVC
Right VENTRICLE

ATRIUM

OLef t
ATRIUM
Left VENTRICLE

Pulmonary veins

LUNGS

SYSTEMIC CAPILLARIES Closure of

Umbilical arteries Stops use of umbilical vessels

Pulmonary arteries

Closure of Ductus arteriosus means that blood expelled from the right ventricle has to go to the lungs Aorta

Post natal changes in various circulatory beds

Coronary Blood flow decreases dramatically as the oxygen content increases.

Cerebral circulation also behaves in the same fashion as coronary circulation.

Post natal changes in various circulatory beds

Skin blood flow is high in utero as the vessels are dilated because the skin is exposed to warm amniotic fluid. Cutaneous vasoconstriction occurs post natally as evaporation from skin starts. Cutaneous flow falls and the vascular resistance increaes.

Post natal changes in various circulatory beds

Hepatic blood flow falls rapidly post natally with reduction in umbilical venous return and then increases as the GI flow is re established. Hepatic blood flow progressively increases after birth and by 7 days after birth reaches a level of 250 ml/minute /100 g by which time there is no flow through ductus venosus.

Changes in Cardiac output

Oxygen consumption increases from 6-8 ml/mt/kg body weight pre natally to 15 20 ml/mt/kg post natally. CVO of fetal lamb is 450 ml/mt/kg. C.O of neonatal lamb is 300 -425 ml/mt/kg.So the CVO will be 600 -850 ml/mt/kg. So the increase is 1.5 to 2 times.

Changes in Cardiac output Mechanisms

Neonate has to increase the metabolism to increase the body temperature as it is exposed to external temperature. Improved diastolic function due to removal of compression by maternal organs and uterus causes increased cardiac filling and hence the cardiac output.

Characteristics of fetal circulatory dynamics

Parallel arrangement of two main arterial systems and their respective ventricles. Mixing of venous return and preferential streaming. High impedance and low flow of pulmonary circulation. Low impedance and high flow of placental circulation. Presence of shunts.

Cardiac output and its distribution Fetal lamb

CVO is 450 ml/kg/wt RV ejects 2/3 and LV ejects 1/3 of CVO UV flow is 200 ml/mt/kg [45% of CVO] Of this,110 ml/mt [24%] passes through DV and 90 ml/mt[21%] passes through hepatic circulation

Cardiac output and its distribution Fetal lamb

Portal venous flow forms 7% and of CVO and abdominal IVC blood forms 30% of CVO. Total venous return to heart from IVC is 315 ml/mt and represents 70% of CVO. Of this 115 ml/mt [25% of CVO] passes through FO and and 200 ml/mt [44%] passes through TV.

Cardiac output and its distribution Fetal lamb

Venous return to heart from SVC is 90 ml/mt/ and represents 21% of CVO most of this passes through tricuspid valve. RV ejects about 300 ml/mt or about 66% of CVO. About 35 ml/mt [8% of CVO] enters the pulmonary circulation

Cardiac output and its distribution Fetal lamb

About 265 ml/mt [60%]passes through ductus arteriosus. LV ejects 150 ml/kg [ 33% ]. Of this,90 ml/mt [20%] distributed to head and upper half and 45 ml/mt [10%]passes through isthmus. 3% of CVO enters coronary circulation.

Cardiac output and its distribution human fetus

Limited data only is available based on doppler studies. Umbilical blood flow is 180 ml/mt /kg of estimated fetal weight. Pulmonary blood flow is estimated to be 75 ml/kg of fetal weight

Cardiac output and its distribution human fetus

CVO appears to be similar to that in lamb, 450 ml/mt/kg fetal weight Ratio of RV output to LV output is only 1.2 to 1.3 as compared to 2:1 in fetal lamb

Venous return to heart

Umbilical vein gives branches to left lobe of liver and then divides into DV and arcuate vien. Arcuate vien joins the portal vein and then gives of branches to right lobe of liver. Left hepatic vein joins the DV at its entry to IVC and Right hepatic vein joins the IVC directly.

Venous return to heart

Right lobe of liver poorly oxygenated portal venous blood and left lobe receives well oxygenated umbilical venous blood. Both lobes receive small contribution of blood from hepatic artery. Saturation of RHV is lower than that of LHV.

Venous return to heart

Posterior and left stream of IVC blood carries oxygenated blood while anterior and right stream carries poorly oxygenated blood. Preferential streaming of DV and LHV blood across the foramen ovale and abdominal IVC and RHV blood across the TV.

Venous return to heart

Eustechian valve helps to direct the IVC blood to cross the foramen ovale. The lower margin of septum secundum [christa dividens] helps to direct the left posterior stream to preferentially across the foramen ovale. SVC blood is directed aross the TV.

Shunts in fetal circulation

Ductus venosus Foramen ovale Ductus arteriosus or aortic isthmus

Shunts in fetal circulation

The blood returning to heart through venacavae and then redistributed to tissues without being delivered to placenta represents effective R to L shunt. The blood which passes through DV and then reaches DA and goes to placenta without getting distributed to tissues represent effective L to R shunt. Combined R to L and L to R shunts forms 33% of CVO.

PULMONARY CIRCULATION
Fetal lung does not serve gas exchange function. PVR is high and PBF is low. This helps to reduce workload of fetal heart.

PULMONARY CIRCULATION
MPA continues as Ductus and RPA and LPA arise as branches. Medial layer is composed of smooth muscle predominantly in small pre acinar and large acinar level arteries. Further branches have no muscular component.

PULMONARY CIRCULATION
PA pressure rises gradually paralleling the rise in aortic pressure. TPR falls gradually but this fall when correlated with rise in lung weight, there is actually an increase in PVR towards term . PBF increases gradually.

PULMONARY CIRCULATION
MPA has forward flow throughout systole with a short period of backflow at end of systole. DA also has forward flow throughout systole. BPA has forward flow only through initial one third of systole followed by back flow through rest of systole and diastole. In humans forward flow is more prolonged.

PULMONARY CIRCULATION
Experiments show fetal PBF increases dramatically in response to increase in maternal PO2. This response is evident only in latter part of gestation. Doppler studies indicate similar changes in humans as well.

PULMONARY CIRCULATION
Fetal pulmonary endothelium behaves in a similar fashion as adult endothelium to vasodilators. Adrenomedullin has a potent and prolonged vasodilatory effect. Leukotriens may be responsible for maintaining high fetal PVR.

PULMONARY CIRCULATION
Breathing at birth is associated with a marked fall in PVR and rise in PBF. PA pressure does not fall as rapidly and remain elevated till the Ductus is widely patent. Once the ductus is closed, PA pressure can vary independent of systemic pressure.

Oxygen exchange function

Higher hemoglobin level in fetus as compared to mother facilitates oxygen uptake by the fetus in the placenta. Oxygen dissociation curve of fetal red cells is shifted to left as compared to adult red cells. HbF has less affinity towards organic phosphates like 2,3 DPG and ATP.

Oxygen exchange function

These phosphates that are present in red cells compete with oxygen for binding to hemoglobin. Affinity of reduced hemoglobin to 2,3 DPG is higher than that of oxyhemoglobin and this facilitates oxygen delivery at tissue site. This is not significant in fetal hemoglobin.

Oxygen exchange function

As CO2 crosses placenta from fetus to mother,it creates a local acidosis. In the face of decreasing Ph,mothers hemoglobin shows less affinity towards Hb and oxygen release is enhanced.[Bohr effect] This supports diffusion of more oxygen across the diffusion membrane to fetus.

Oxygen exchange function

As O2 is released,maternal Hb acts as a buffer that removes H+ from local environment. This encourages production of bicarbonate from H2O and CO2 thereby reducing local PC02 and facilitating diffusion of CO2 from fetus.

Post natal changes

Gas exchange function is transferred from placenta to the lungs. Separation of systemic and pulmonary circulations Increased metabolism to maintain body temperature and hence increased cardiac output.

Post natal changes in various circulatory beds

Coronary Blood flow decreases dramatically as the oxygen content increases.

Cerebral circulation also behaves in the same fashion as coronary circulation.

Post natal changes in various circulatory beds

Skin blood flow is high in utero as the vessels are dilated because the skin is exposed to warm amniotic fluid. Cutaneous vasoconstriction occurs post natally as evaporation from skin starts. Cutaneous flow falls and the vascular resistance increaes.

Post natal changes in various circulatory beds

Hepatic blood flow falls rapidly post natally with reduction in umbilical venous return and then increases as the GI flow is re established. Hepatic blood flow progressively increases after birth and by 7 days after birth reaches a level of 250 ml/minute /100 g by which time there is no flow through ductus venosus.

Changes in Cardiac output

Oxygen consumption increases from 6-8 ml/mt/kg body weight pre natally to 15 20 ml/mt/kg post natally. CVO of fetal lamb is 450 ml/mt/kg. C.O of neonatal lamb is 300 -425 ml/mt/kg.So the CVO will be 600 -850 ml/mt/kg. So the increase is 1.5 to 2 times.

Changes in Cardiac output Mechanisms

Neonate has to increase the metabolism to increase the body temperature as it is exposed to external temperature. Improved diastolic function due to removal of compression by maternal organs and uterus causes increased cardiac filling and hence the cardiac output.

Changes in Cardiac output Mechanisms

Perinatal but not post natal increase in thyroid hormones is the principal mechanism for increase in cardiac output. Improvement in myocardial growth and maturation brought about by cortisol may also play important role.

Changes in hemoglobin and tissue oxygen delivery

Human new born has a high hemoglobin level (about 16g/dl) so that the oxygen carrying capacity is quiet high and the total amount of oxygen transported to tissues is quiet high. Since the Hb F levels are still high facilitation at tissue site is not as great as in adults. Over the first 8-10 weeks after the birth,Hb concentration falls to 10-11 g/dl. This is accompanied by loss of Hb F and almost 100% is adult type.

Regulation of fetal circulation

Arterial baroreceptors are funtional in fetus from early in the gestation Near term, it is as sensitive as adults in fetal lambs. Chemoreceptors are active only in latter part of gestation.

Fetal circulation in pathological conditions

Fetal circulation in pathological conditions

Development of a structural abnormality will modify the fetal circulation. This will affect the development of other components and can lead to other defects. The impact of a defect will depend on its severity and time of gestation at which it occurs.

Fetal circulation in pathological conditions

Many of the defects, though it modifies the circulation, will not significantly affect fetal perfusion and hence the growth and development. This is because of the presence of shunts and mixing of blood. Fetus tolerates the obstructive lesions very much. Fetal circulation is jeopardized by regurgitant lesions and myocardial disease.

Septal defects
They in general do not modify the fetal circulation significantly. VSD may have a transient left to right shunt in systole. In OP ASD, due to close proximity of defect with TV, more than normal amount of SVC blood may enter the LA.

Septal defects
In atrioventricular septal defects, the obligatory flow from LV to RA will result in decrease in LV output and an increase in RV output. This will reduce the flow across the isthmus and can predispose to coarctation. It is the degree of severity of AV valve lesion and regurgitation which will determine the outcome.

LVOT Obstruction
Severe obstruction developing early result in a small LV with an increased mass.

RV is able to compensate fully if LVOTO develops slowly.

LVOT Obstruction
SVC flow courses normally. Majority of IVC blood flow crosses TV to RV. Flow across the ductus increases.

PBF has higher than normal saturation.

LVOT obstruction
Decrease in saturation between DA and AA. LV systolic pressure increases slightly but not EDP. A retrograde flow in arch and ascending aorta indicates severe obstruction.

62 75/50

75/4

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90/ 5 60

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70

Aortic arch abnormalities

Most of the alteration in the circulation are due to co existing intra cardiac defects. Common features are, reduced flow in to ascending aorta, increased flow in to the pulmonary trunk and greater proportion of CVO carried across ductus to descending aorta. The decreased volume loading of LV may possibly interfere with its development.

Mitral and aortic atresia

All blood must pass through RV and ductus has to provide for both AA and DA blood flow. Complete mixing of blood occurs in RA and saturation in PA,AA and DA are all same. If the foramen ovale is sufficiently large and ductus accomodates whole of systemic blood flow, there will be no significant interference with intrauterine development and survival.

70/40 60 70/2 60 60

40

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Mitral and aortic atresia

If the foramen ovale is restrictve, severe pulmonary venous hypertension develops. If the ductus does not enlarge to accommodate the whole of systemic blood flow increased blood flow to lungs and pulmonary hypertension develops. Both these can lead to increased development of smooth muscle in the pulmonary vasculature.

RVOTO with intact IVS

In rapidly developing RVOTO,RV and LV cannot compensate for and the CVO falls. If RVOTO developing slowly,both LV and RV can compensate for and CVO is maintained. In pulmonary atresia, total cardiac output is carried by the left heart.

63 63 63 100/4 63 70/3 40

70

RVOTO with intact IVS

In pulmonary atresia, all systemic venous blood is carried to left side through foramen ovale and all blood supply to DA is provided through isthmus. Larger than normal foramen ovale, left sided chambers,AA and aortic isthmus.

RVOTO with intact IVS If severe RVOTO develops early in gestation,the flow through the ductus is reversed and carries only 8 to 10 % of cardiac output. The ductus will be narrower and will make an acute inferior angle with aorta. The ductus will remain patent for longer than normal duration.

RVOTO with intact IVS

If the fetus develops significant TR,RV pressure remains low and myocardial sinusoids and coronary fistulae do not develop. If TR does not develop,significant RV systolic pressure develops and if occurs early in gestation, intramyocardial sinusoids and coronary fistulae develop.

TAPVC
Usually does not affect the development of fetus. If whole of PV return drains to SVC,LV will be totally free of PV blood and hence will be of higher saturation. Left atrium and left ventricle will be relatively small in TAPVC.

TOF and related disorders

Does not appear to affect fetal circulation adversely. The volume and direction of flow across the PA and ductus are dependant on the severity of obstruction. Total flow through the ductus will be reduced considerably.

TOF and related disorders

This can markedly reduce the diameter of fetal ductus and also reduce the development of smooth muscle in its wall. If blood flows from aorta to PA in fetal life,the orientation of ductus changes and it forms an acute inferior angle with aorta. AA and the isthmus carries large than normal amount of blood and they tend to be larger.

70/45 63

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TOF with absent PV

Ductus is frequently either atretic or not developed. RV would be subjected to both volume and pressure overload and can develop in utero. Significant pulmonary regurgitation can seriously affect perfusion of pulmonary vessels and cause abnormal development of intrapulmonary vessels.

Aortopulmonary transposition
Compatible with fetal survival and normal intrauterine development. Does not affect the pattern of venous return. Blood with higher oxygen saturation will go to lungs. This will reduce the PVR and hence increase in PBF.

Aortopulmonary transposition
This will reduce the blood flow across the ductus and increases the flow across the isthmus. Blood with lower oxygen saturation perfuses coronary and cerebral circulation. Hence cerebral and coronary blood flow are increased considerably.

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TGA with VSD

Bi directional shunting occur depending on after load of each ventricle.

The difference in saturation between AA and DA will be lesser.

TGA with VSD and PS

Almost complete admixture of SVC and IVC streams in RV. AA and DA will have similar oxygen saturations. Blood flow in the ductus will be from aorta to PA.

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Truncus arteriosus
Various degree of mixing occurs just above the semilunar valve. Degree of mixing depends on morphology.In type 1,there is differential streaming of blood and in others there will be complete mixing. Ductus is usually small or absent and increased flow traverses through isthmus and it is large.

Ebsteins anomaly
Severe TR can manifest as in utero cardiac failure especially if foramen ovale is restrictive. Marked enlargement of RA and atrialised RV can cause septal displacement and compromise LV output. Functional pulmonary atresia can result and ductal flow may be reversed.

Ebsteins anomaly
Marked enlargement of right atrium can cause pulmonary hypoplasia Severe TR alters the preferential drainage of venacaval blood and causes complete mixing of blood in right atrium.

Tricuspid atresia
All of the venous return traverses foramen ovale and it is considerably larger than normal . Complete admixture of blood in the left atrium It is compatible with normal intrauterine development and survival.

Tricuspid atresia
If IVS is intact, whole PBF is from aorta through ductus and ductal flow is lesser than normal. 75% of combined VO traverses the isthmus and it tends to be larger. In the presence of VSD,the flow pattern is decided by the size of the defect and presence of pulmonary stenosis.