Fetal circulation
Fetal circulation, fetal haemoglobin and oxygen transfer across the placenta
The fetus lives at a PO2 of about 30 mmHg, so it relies on shunts that send the best blood to the heart and brain, on a high-affinity haemoglobin, and on a placenta that exchanges gases by diffusion. At birth the shunts close within hours to weeks. CPSP asks about the route of fetal blood, the changes at birth, the properties of HbF and the double Bohr and Haldane effects.
Route of fetal blood
- Umbilical vein carries the best-oxygenated blood in the fetus, yet its PO2 is only about 30 mmHg (4 kPa), saturation about 80%.
- About half bypasses the liver through the ductus venosus into the IVC; the rest passes through the liver via the left portal vein.
- In the right atrium the crista dividens and IVC valve direct this stream through the foramen ovale to the left atrium, left ventricle and ascending aorta, so the coronary and carotid arteries get the best blood.
- SVC blood (from head and arms) goes mainly to the right ventricle and pulmonary trunk; about 90% of it passes through the ductus arteriosus into the descending aorta, because pulmonary vascular resistance is high (fluid-filled lungs, hypoxic vasoconstriction). The lungs receive only about 10% of right ventricular output.
- So blood in the ascending aorta is better oxygenated than in the descending aorta. The ventricles work in parallel; the right ventricle pumps about 60% of combined output.
- Two umbilical arteries (from the internal iliacs) return blood to the placenta.
Changes at birth
| Event | Consequence |
|---|---|
| Cord clamped | Low-resistance placenta removed: systemic vascular resistance rises at once; ductus venosus flow stops |
| First breaths | Lungs expand, alveolar PO2 rises: pulmonary vascular resistance falls, pulmonary flow rises |
| Left atrial pressure exceeds right | Flap of the foramen ovale closes (functional at once, anatomical over months; patent in about a quarter of adults, allowing paradoxical embolism) |
| Rising PaO2 and falling prostaglandin E2 (placenta gone, lungs clear it) | Ductus arteriosus constricts: functional closure in 1–2 days, anatomical in weeks |
- In very preterm babies the ductus muscle responds poorly to oxygen and stays sensitive to PGE2, so a patent ductus (bounding pulses, continuous murmur) is common; COX inhibitors help close it, prostaglandin E1 keeps it open in duct-dependent heart lesions.
- A persisting ductus venosus lets portal blood bypass the liver: raised ammonia and galactose.
- Pulse oximetry: the right hand is pre-ductal (its artery arises before the ductus); a foot is post-ductal.
| Fetal structure | Adult remnant |
|---|---|
| Umbilical vein (left) | Ligamentum teres in the lower edge of the falciform ligament |
| Ductus venosus | Ligamentum venosum |
| Foramen ovale | Fossa ovalis |
| Ductus arteriosus (from the left sixth arch artery) | Ligamentum arteriosum |
| Umbilical arteries | Medial umbilical ligaments; proximal parts remain as superior vesical arteries |
Fetal haemoglobin
- HbF = alpha2 gamma2. Gamma chains bind 2,3-BPG poorly, so the dissociation curve is shifted left (P50 about 19 mmHg against 27 mmHg for HbA): higher affinity, loading oxygen at low PO2.
- Fetal haemoglobin concentration is high (about 17 g/dL at term), so each litre carries more oxygen; fetal cardiac output per kilogram is also high.
- After birth gamma chains are replaced by beta chains over about six months, so beta-thalassaemia major is silent at birth and presents at 3–7 months with pallor, failure to thrive and splenomegaly.
Gas exchange across the placenta
- Oxygen and CO2 cross by simple diffusion; transfer is flow-limited, depending mainly on uterine and umbilical blood flow. In pre-eclampsia, unremodelled narrow spiral arteries reduce maternal flow and cause fetal hypoxia even with a normal villous membrane.
- Double Bohr effect: fetal blood gives up CO2 (pH rises, affinity rises, takes up oxygen) while maternal blood gains CO2 (affinity falls, releases oxygen).
- Double Haldane effect: maternal blood, as it deoxygenates, can carry more CO2; fetal blood, as it oxygenates, releases CO2.
- Maternal hyperventilation (PaCO2 about 30 mmHg) steepens the CO2 gradient from fetus to mother.
- Carbon monoxide from smoking crosses freely; fetal carboxyhaemoglobin exceeds the mother's, reducing oxygen content and shifting the curve left so less oxygen is released to tissues.
- Umbilical artery Doppler: diastolic flow normally rises with gestation as placental resistance falls. Absent end-diastolic flow means raised placental vascular resistance (obliterated villous vessels).
Other placental transfer
| Mechanism | Examples |
|---|---|
| Simple diffusion | O2, CO2, water, urea, lipid-soluble drugs, anaesthetic gases |
| Facilitated diffusion | Glucose (GLUT1; saturable) |
| Active transport | Amino acids, calcium, iron, iodide |
| Receptor-mediated transcytosis | IgG (neonatal Fc receptor) |
| Little or none | IgM, insulin, heparin, large proteins, TSH |
Remember The fetus wins oxygen with left-shifted HbF, a high haemoglobin and the double Bohr effect.
Exam trap The umbilical vein, not the umbilical artery, carries oxygenated blood in the fetus.
Exam trap Ductus closure is triggered by oxygen plus falling prostaglandin E2; giving prostaglandin keeps it open.
Test yourself on this topic
5 of the 28 questions in our bank on this topic. Choose an answer to see why every option is right or wrong.
Cord blood from a healthy term baby has a haemoglobin of 17 g/dL. Besides the higher oxygen affinity of HbF, how does this level help the fetus live at a low PO2?
Answer: Carries more oxygen per litre of blood
Oxygen content depends on haemoglobin concentration and saturation. The fetus has a higher haemoglobin concentration than the adult, about 17 g/dL, driven by fetal erythropoietin in the relatively hypoxic intrauterine environment. Together with the left-shifted HbF curve and a high fetal cardiac output per kilogram, it allows adequate oxygen content and delivery despite a PO2 of about 30 mmHg. After birth, when oxygen rises, erythropoiesis falls and haemoglobin drops to its physiological nadir at 2–3 months.
Fetal oxygen carriage
- Hb about 17 g/dL
- More oxygen content
- HbF curve left-shifted
- High cardiac output per kg
Remember More haemoglobin makes up for low PO2.
Exam trap A cord haemoglobin of 17 g/dL is normal, not polycythaemia.
Why the other options are wrong
- Lowers blood viscosity in the villi Higher haematocrit increases viscosity.
- Raises 2,3-BPG in fetal red cells HbF binds 2,3-BPG poorly; this is not the effect.
- Shifts the fetal curve to the right The fetal curve is left-shifted.
- Increases fetal plasma volume Not the benefit.
Newborn pulse oximetry screening for critical congenital heart disease compares the right hand with a foot. Why is the right hand used for the pre-ductal reading?
Answer: Its artery arises before the ductus
The right subclavian artery arises from the brachiocephalic trunk, proximal to the ductus arteriosus insertion, so the right hand reflects pre-ductal aortic blood. The lower limbs receive post-ductal blood from the descending aorta. A lower foot saturation shows right-to-left flow through the ductus, as in coarctation, hypoplastic left heart or persistent pulmonary hypertension. The left subclavian may arise close to or beyond the ductus, so the left arm is not reliably pre-ductal.
Pre- and post-ductal
- Right hand: pre-ductal
- Feet: post-ductal
- Left arm: unreliable
- Foot lower: ductal right-to-left shunt
Remember Right hand before the duct; feet after it.
Exam trap The left subclavian can arise opposite the ductus, so the left hand is not a safe pre-ductal site.
Why the other options are wrong
- It has the best capillary perfusion Not the reason.
- It is supplied by the left ventricle only Both ventricles' output mixes in the aorta.
- It is unaffected by the foramen ovale Foramen ovale shunting lowers all sites.
- It is closest to the heart Proximity is not the reason.
A 2-month-old has raised blood ammonia and galactose, with normal liver enzymes. Doppler shows that the ductus venosus has failed to close after birth. Why are these substances raised?
Answer: Portal blood bypasses the liver
In the fetus, the ductus venosus carries blood from the umbilical vein and left portal vein directly to the IVC, bypassing the liver sinusoids. After birth it normally closes within days to become the ligamentum venosum. If it stays open, portal venous blood from the gut shunts past the liver, so substances such as ammonia and galactose escape hepatic clearance. Liver enzymes stay normal because hepatocytes are not damaged.
Patent ductus venosus
- Ductus venosus bypasses the liver
- Normally closes in days
- Patent: portosystemic shunt
- High ammonia, galactose
Remember An open fetal bypass after birth lets gut blood skip the liver.
Exam trap Normal liver enzymes with high ammonia suggest a shunt, not liver cell damage.
Why the other options are wrong
- Umbilical venous blood enters the brain The umbilical circulation stops at birth.
- Hepatocytes are poisoned by oxygen Not the mechanism.
- Hepatic arterial flow is lost Hepatic arterial flow is preserved.
- Bile flow is obstructed Bile drainage is not affected.
A woman with severe pre-eclampsia at 32 weeks has a growth-restricted, hypoxic fetus. Placental histology shows narrow, unremodelled spiral arteries but a normal villous membrane. Oxygen crosses the placenta by simple diffusion. What mainly limits oxygen delivery to this fetus?
Answer: Reduced uteroplacental blood flow
Oxygen is a small, lipid-soluble molecule that equilibrates rapidly across the thin villous membrane, so its transfer is flow-limited rather than diffusion-limited. The amount delivered depends mainly on maternal blood flow into the intervillous space and fetal blood flow through the villi. Failure of trophoblast to remodel the spiral arteries in pre-eclampsia keeps them narrow and reactive, reducing uteroplacental flow. The membrane here is normal, and maternal PO2 is usually normal.
Placental oxygen transfer
- Moves by simple diffusion
- Transfer is flow-limited
- Depends on uteroplacental flow
- Unremodelled spiral arteries: hypoxic fetus
Remember For oxygen, flow matters more than the membrane.
Exam trap Oxygen transfer is limited by blood flow, not by the barrier, unless the membrane is diseased.
Why the other options are wrong
- Thickened placental membrane The membrane is normal here.
- Lack of oxygen carrier proteins Oxygen moves by diffusion, without carriers.
- Saturation of active transporters Oxygen does not use active transport.
- Low maternal arterial PO2 Usually normal in pre-eclampsia.
A preterm baby has a continuous murmur from a patent ductus arteriosus. From which embryonic artery does the ductus arteriosus develop?
Answer: Left sixth pharyngeal arch artery
The sixth pharyngeal arch arteries form the proximal pulmonary arteries. On the left, the distal part of the sixth arch artery persists as the ductus arteriosus, linking the pulmonary trunk to the aorta. On the right, the distal part regresses, which is why the right recurrent laryngeal nerve hooks higher, around the subclavian artery. The left fourth arch forms part of the aortic arch, and the third arches form the carotids.
Ductus arteriosus origin
- From left sixth arch artery
- Proximal sixth arches: pulmonary arteries
- Right distal sixth regresses
- Left recurrent nerve hooks under the ductus
Remember Sixth arch on the left keeps its duct.
Exam trap The fourth arch forms the aortic arch; the ductus comes from the sixth.
Why the other options are wrong
- Right sixth pharyngeal arch artery Its distal part regresses.
- Left fourth pharyngeal arch artery Forms part of the aortic arch.
- Third pharyngeal arch arteries Form the common and proximal internal carotids.
- Left dorsal aorta below the arch Not the origin of the ductus.
Where this sits in the CPSP syllabus
- Obstetrics & Gynaecology, Paper 2: Reproduction, pregnancy and labour, Fetal circulation, fetal haemoglobin and oxygen transfer across the placenta
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