Foetal Circulation

The Diagram

Step-by-Step Blood Flow

1. Placenta → Umbilical Vein

• Oxygenated, nutrient-rich blood leaves the placenta via the umbilical vein (~80% O₂ saturation - the highest in the fetal circulation).
• The umbilical vein travels through the umbilical cord and enters the fetal abdomen at the umbilicus.

2. Liver Level - First Shunt: Ductus Venosus

• On reaching the liver, the blood splits:
  • ~50% bypasses the liver directly via the ductus venosus → enters the inferior vena cava (IVC).
  • ~50% enters the portal system → perfuses hepatic sinusoids → drains via hepatic veins into the IVC.
• A physiologic sphincter near the ductus venosus regulates this split - during uterine contractions (high umbilical flow), the sphincter constricts to prevent cardiac overload.
• In the IVC, this blood mixes with deoxygenated blood from the lower limbs, pelvis, and kidneys - first mixing point (Point II per Langman's).

3. Right Atrium - Second Shunt: Foramen Ovale

• Blood from the IVC enters the right atrium. Here it is guided by the crista dividens (inferior edge of the septum secundum):
  • Most of the relatively well-oxygenated IVC blood is directed through the foramen ovale directly into the left atrium, bypassing the lungs entirely.
  • A small amount is blocked by the crista dividens and stays in the right atrium, where it mixes with poorly oxygenated blood from the SVC (returning from the head and upper limbs).

4. Left Atrium → Left Ventricle → Ascending Aorta

• Blood from the foramen ovale enters the left atrium, mixes with a small volume of blood from the pulmonary veins (the fetal lungs extract oxygen rather than add it).
• From the left ventricle it enters the ascending aorta.
• The coronary arteries and carotid arteries branch first from the ascending aorta - so the heart and brain receive the best-oxygenated blood available.

5. Right Ventricle - Third Shunt: Ductus Arteriosus

• The small amount of blood remaining in the right atrium (from the SVC + some IVC blood) passes into the right ventricle → into the pulmonary trunk.
• In fetal life, pulmonary vascular resistance is high (hypoxic pulmonary vasoconstriction, fluid-filled lungs). Only ~10% of right ventricular output actually goes to the lungs.
• The rest (>85%) passes through the ductus arteriosus (connecting the pulmonary trunk to the descending aorta), bypassing the lungs.

6. Descending Aorta → Umbilical Arteries → Back to Placenta

• Blood in the descending aorta (now lower O₂ saturation ~58%) supplies the abdominal organs and lower limbs.
• It then flows into the internal iliac arteries → umbilical arteries → back through the umbilical cord → to the placenta for re-oxygenation.

The Three Key Shunts - Summary

Where Mixing Occurs (Langman's 5 Points)

1. Liver - umbilical vein blood mixes with portal blood
2. IVC - mixes with deoxygenated blood from lower limbs
3. Right atrium - mixes with SVC blood from head/arms
4. Left atrium - mixes with small amount of pulmonary venous blood
5. Descending aorta - at the entry of the ductus arteriosus

Changes at Birth (Neonatal Transition)

1. Clamping of the Umbilical Cord

• Removes the low-resistance placental circuit → systemic vascular resistance rises sharply.
• Right atrial pressure falls (placental return stops).

2. First Breath - Lung Expansion

• Lungs fill with air → pulmonary vascular resistance drops dramatically (due to mechanical expansion and rise in pO₂).
• Pulmonary blood flow increases markedly → more blood returns to the left atrium → left atrial pressure rises.

Closure of the Shunts

Neonatal Circulation

Why This Design Makes Sense

• The brain and heart need the most oxygen - they receive the best blood (via ascending aorta).
• The lower body and placenta receive mixed/deoxygenated blood - acceptable, since the placenta will re-oxygenate it.
• The liver receives some well-oxygenated blood (for metabolic needs) but also has ~50% bypassed (via ductus venosus) to avoid overloading the heart.
• The lungs are essentially bypassed entirely - no point perfusing them when they are fluid-filled and not exchanging gas.

Circulatory Changes at Birth

The Two Triggering Events

1. Cessation of Placental Blood Flow

• Cord clamping removes the large, low-resistance placental vascular bed.
• Systemic vascular resistance rises sharply.
• Blood flow returning via the IVC drops → right atrial pressure falls.

2. Lung Expansion (First Breath)

• Aeration of the alveoli causes:
  • Dramatic drop in pulmonary vascular resistance (from mechanical stretching of pulmonary arteries + rising O₂ tension causing vasodilation).
  • Marked increase in pulmonary blood flow - the pulmonary arteries, which were thick-walled and vasoconstricted in fetal life, progressively thin out.
  • More blood now flows through the lungs → more returns to the left atrium → left atrial pressure rises.

Closure of Each Shunt

Foramen Ovale

• The rise in LA pressure presses the septum primum against the septum secundum, like a flap valve snapping shut.
• Functional closure: at birth (within the first breath).
• Anatomical closure: fusion of the two septa over weeks to months (~1 year).
• In 20% of adults, complete anatomical fusion never occurs - this is called a probe patent foramen ovale (PFO), which is usually clinically silent but can be a route for paradoxical embolism.
• In the first few days, crying can momentarily raise RA pressure and cause a brief right-to-left shunt, producing transient cyanosis in the newborn - this is normal.
• Adult remnant: Fossa ovalis

Ductus Arteriosus

• As pulmonary resistance drops below systemic resistance, blood flow through the ductus reverses direction (now aorta → pulmonary trunk) - this is why left-to-right shunting occurs before it closes.
• Mechanism of closure: The lungs release bradykinin during initial inflation. Bradykinin, combined with the rise in arterial pO₂, causes smooth muscle contraction in the ductus wall.
• Functional closure: within hours of birth.
  • At 24 hours: 20% of ducts functionally closed.
  • At 48 hours: 82% closed.
  • By 96 hours: 100% in full-term neonates.
• Anatomical closure (fibrous obliteration): 1-3 months.
• Premature neonates have immature smooth muscle and are less sensitive to O₂/bradykinin - hence patent ductus arteriosus (PDA) is common in prematurity, treated with indomethacin (prostaglandin inhibitor) or surgical ligation.
• Adult remnant: Ligamentum arteriosum

Ductus Venosus

• The ductus venosus sphincter constricts within hours of cord clamping.
• All portal blood must now pass through the hepatic sinusoids - the liver is no longer partially bypassed.
• Functional closure: within hours of birth.
• Anatomical closure: few weeks.
• Adult remnant: Ligamentum venosum (visible on the visceral surface of the liver, between the left lobe and caudate lobe).

Umbilical Vessels

• Close within a few minutes of birth by smooth muscle contraction - triggered by thermal stimuli (cold), mechanical stimuli (handling), and the rise in arterial pO₂.
• Anatomical obliteration by fibrous proliferation: 2-3 months.
• Adult remnants:
  • Distal portions → Medial umbilical ligaments (visible on the inner anterior abdominal wall).
  • Proximal portions remain patent as the Superior vesical arteries (supplying the bladder).

• Closes shortly after the umbilical arteries. Blood from the placenta can still enter the newborn for a short time after birth if the cord is not immediately clamped.
• Adult remnant: Ligamentum teres hepatis (round ligament of the liver), running in the free edge of the falciform ligament.

Summary Table - Foetal Structures and Their Adult Derivatives

Ventricular Wall Changes

• In the fetus, the right ventricular wall is thicker than the left - because the RV has been pumping against high pulmonary resistance.
• After birth, the LV now drives the systemic circulation (high resistance) while the RV pumps against the now-low pulmonary resistance.
• By end of the first month: the LV wall becomes thicker than the RV wall.
• The RV wall gradually thins due to its reduced workload.

Clinical Relevance - When Shunts Fail to Close

Changes at Birth - A Sequential Physiological Analysis

1. The First Breath

What is in the lungs before birth?

The "Vaginal Squeeze"

• Babies delivered by caesarean section miss this squeeze and retain more lung fluid → Transient Tachypnoea of the Newborn (TTN) is more common.
• Preterm neonates also miss the benefit of full vaginal squeeze.

What triggers breathing?

• Sensory stimulation: cold air, light, sound, touch, pain, cord clamping
• Mild hypoxia and acidosis from the birth process - act as chemical respiratory stimuli
• Outward recoil of the chest after delivery - the chest wall springs outward, passively drawing air in
• NOT primarily hypoxia in a normal labour (Ganong's)

The mechanics

• The first breath requires a very large negative intrathoracic pressure of -30 to -50 mmHg to overcome:
  • Surface tension of fluid in the alveoli
  • Resistance of airway fluid
  • Elastic recoil of the lungs
• Surfactant is essential here - it reduces alveolar surface tension, prevents alveolar collapse on expiration, and stabilises lung expansion. It is produced from ~30 weeks (adequate amounts by ~34 weeks).
• Respiratory efforts normally begin within 30 seconds of birth and become sustained within 90 seconds.

Immediate result of lung expansion

• Alveolar and arterial pO₂ rises sharply
• This rising O₂ tension is the most potent stimulus for pulmonary arterial vasodilation - mediated through nitric oxide (NO) production
• Pulmonary vascular resistance (PVR) falls to less than 20% of its in utero value after just the first few breaths

2. Flow of Blood to the Lungs

Before birth

• Hypoxia (low alveolar pO₂ causes hypoxic pulmonary vasoconstriction)
• High CO₂, low pH
• Physical compression of vessels by fluid-filled alveoli

After first breath

• Lung expansion + rising pO₂ → NO-mediated vasodilation of pulmonary arterioles
• PVR drops dramatically
• Right ventricular output now floods into the pulmonary circulation
• Pulmonary blood flow increases 4-5 fold within minutes
• Pulmonary artery walls progressively thin out (from mechanical stretching by the expanded lungs)
• More blood returns to the left atrium via the pulmonary veins → left atrial pressure rises

3. Closure of the Foramen Ovale

Foetal state

• RA pressure > LA pressure (because the IVC delivers large volumes of oxygenated umbilical blood to the right side)
• This pressure gradient holds the foramen ovale open, directing blood left-to-right (RA → LA)

At birth - two simultaneous pressure changes

• LA pressure now exceeds RA pressure
• The septum primum (which acts as a flap valve) is pushed against the septum secundum from the left side, mechanically sealing the foramen ovale shut
• Functional closure: at birth, with the first few breaths
• Anatomical closure: weeks to months (fusion of septa); takes up to 1 year
• In 20% of adults: complete anatomical fusion never occurs → probe patent foramen ovale (PFO) - usually silent, but risk of paradoxical embolism/cryptogenic stroke
• In the first days of life, crying briefly raises RA pressure, temporarily reopening the foramen → physiological transient cyanosis in newborns

4. Reversal of Blood Flow in the Ductus Arteriosus

Foetal direction

• Pulmonary trunk → Descending aorta (right-to-left)
• Driven because PVR > SVR, so blood took the path of least resistance away from the lungs

At birth - pressure reversal

• PVR drops dramatically (first breath)
• SVR rises (cord clamping removes low-resistance placenta)
• Now SVR > PVR → blood flow in the ductus arteriosus reverses
• New direction: Aorta → Pulmonary trunk (left-to-right)
• This left-to-right shunt persists briefly while the ductus remains open
• The right ventricle's output now flows preferentially into the pulmonary trunk rather than the aorta

5. Closure of the Ductus Venosus

Mechanism

• Cord clamping removes umbilical venous return - there is no longer high-pressure blood flowing from the placenta
• The physiologic sphincter at the ductus venosus constricts almost immediately
• All portal blood must now pass through the hepatic sinusoids - the liver loses its partial bypass
• Functional closure: within hours of cord clamping
• Anatomical closure: 1-3 weeks (fibrotic obliteration)
• Adult remnant: Ligamentum venosum (visible in the groove between the left lobe and caudate lobe of the liver)

6. Closure of the Ductus Arteriosus

What keeps it open in foetal life?

1. Low pO₂ of blood flowing through it (foetal blood is relatively hypoxic)
2. Prostaglandins - locally produced PGE₂ and prostacyclin (PGI₂) cause smooth muscle relaxation and keep the ductus open. Hypoxia promotes their local synthesis.

What triggers closure at birth?

• When pO₂ of blood passing through the ductus reaches ~50 mmHg, smooth muscle of the ductus wall contracts
• O₂ acts both directly on smooth muscle and indirectly by:
  • Stimulating release of bradykinin from the newly inflated lungs
  • Suppressing local PGE₂ synthesis (O₂ inhibits cyclooxygenase activity)

• Released from the lungs during initial inflation
• Has potent contractile effects on ductal smooth muscle
• Its action is dependent on the high O₂ content of aortic blood

• Birth inhibits cyclooxygenase → PGE₂ and PGI₂ synthesis falls → vasodilatory tone is lost
• This is why indomethacin (COX inhibitor) closes a PDA in premature neonates

Timeline of closure

• Adult remnant: Ligamentum arteriosum (connects pulmonary trunk to aortic arch)

Why prematurity causes PDA

• Immature smooth muscle is less responsive to O₂ and bradykinin
• PGE₂ production is higher relative to ductal responsiveness
• Treatment: indomethacin or ibuprofen (COX inhibitors) - block PGE₂ → ductal constriction
• If medical treatment fails: surgical/catheter ligation

The Full Sequence as a Timeline

Birth
  │
  ├─ Vaginal squeeze clears lung fluid
  │
  ├─ Sensory stimuli + mild hypoxia → FIRST BREATH (within 30 sec)
  │     │
  │     ├─ pO₂ rises → NO production → pulmonary vasodilation
  │     ├─ PVR falls to <20% of fetal value
  │     │
  │     ├─ PULMONARY BLOOD FLOW ↑↑↑ (4-5×)
  │     │     └─ LA pressure rises
  │     │
  │     ├─ Cord clamping → umbilical return lost → RA pressure falls
  │     │
  │     ├─ LA > RA pressure → FORAMEN OVALE closes (functional)
  │     │
  │     ├─ PVR < SVR → DA flow REVERSES (aorta → pulmonary trunk)
  │     │
  │     ├─ ↑pO₂ + bradykinin (from inflated lungs) → DUCTUS ARTERIOSUS constricts
  │     │     + PGE₂ synthesis falls (COX inhibited) → closes over hours-days
  │     │
  │     └─ Umbilical flow stops → DUCTUS VENOSUS sphincter constricts → closes
  │
  └─ Result: Parallel (fetal) circulation → Serial (adult) circulation

What Happens if This Transition Fails?

• Hypoxia maintains high PVR
• PGE₂ production continues → ductus stays open
• Right-to-left shunting persists → more hypoxia → more shunting
• This vicious cycle is Persistent Pulmonary Hypertension of the Newborn (PPHN) - a life-threatening emergency
• Treatment: O₂, inhaled NO, surfactant, possibly ECMO

Changes at Birth - Before vs After

BEFORE birth → AFTER birth

Before birth: 3 shunts bypass the lungs and liver

After birth: all shunts closed, lungs now oxygenate the blood

The Big Picture First

1. 🫁 The First Breath

• ~90 mL of fluid (not air)
• Pulmonary vessels tightly squeezed shut (high resistance)

• Cold air on skin, touch, sound, light
• Mild drop in O₂ at delivery
• The chest wall springs outward after the baby exits → passively sucks air in
• Requires a strong suction effort: -30 to -50 mmHg (much greater than normal adult breathing)

• Alveoli expand → lung fluid is squeezed out (or reabsorbed)
• O₂ rises in the blood → pulmonary blood vessels relax and open up
• Pulmonary vascular resistance (PVR) falls to <20% of foetal levels in just a few breaths

⚠️ C-section babies miss the "vaginal squeeze" that clears lung fluid → more prone to Transient Tachypnoea of the Newborn (TTN)

⚠️ Premature babies lack surfactant (produced from ~34 weeks) → alveoli collapse after each breath → Respiratory Distress Syndrome (RDS)

2. 🩸 Blood Flow to the Lungs

• Only ~10% of blood went to the lungs
• 90% bypassed via the ductus arteriosus

Lungs expand
    ↓
O₂ rises → Nitric Oxide released → pulmonary vessels DILATE
    ↓
Pulmonary resistance falls sharply
    ↓
Blood FLOODS the lungs (4-5× increase)
    ↓
More blood returns to LEFT ATRIUM via pulmonary veins
    ↓
LEFT ATRIAL PRESSURE RISES ← this drives the next two closures

3. ❤️ Closure of the Foramen Ovale

• Right atrium had higher pressure than left (IVC delivering lots of umbilical blood)
• Blood pushed the flap open: RA → LA

• LA pressure now > RA pressure
• The flap (septum primum) gets pushed shut from the left side - like a door blown closed by wind
• Functional closure: minutes after birth
• Permanent fusion: weeks to months

⚠️ In 20% of people, the flap never fully fuses → Patent Foramen Ovale (PFO) - usually harmless, but can allow blood clots to cross from right to left → stroke

4. 🔄 Reversal of Blood Flow in the Ductus Arteriosus

• This reversal is temporary - it lasts only while the ductus is still open
• It actually helps send more blood to the lungs during the transition
• Then the ductus constricts and closes (step 6)

5. 🏥 Closure of the Ductus Venosus

• Cord is clamped → high-pressure umbilical blood flow stops
• No flow = no reason to stay open
• The sphincter at its entrance constricts
• All blood from the gut must now pass through the liver

6. 🔒 Closure of the Ductus Arteriosus

• Low O₂ in foetal blood
• Prostaglandins (PGE₂, PGI₂) - these relax the duct wall and keep it open

First breath
    ↓
O₂ in blood RISES
    ↓
Two effects:
  ① O₂ directly contracts the duct wall muscle
  ② O₂ triggers release of BRADYKININ from lungs
       → bradykinin = powerful muscle contractor
    ↓
Also: Prostaglandin production FALLS
  (O₂ inhibits the enzymes that make PGE₂)
    ↓
Ductus arteriosus CONSTRICTS and closes

⚠️ Premature babies: Duct muscle is immature → doesn't respond to O₂/bradykinin → Patent Ductus Arteriosus (PDA)

• Hear a continuous "machinery murmur"
• Treatment: Indomethacin (blocks prostaglandin → duct constricts) or surgical ligation

All 6 Events as One Flowchart

BIRTH
  │
  ▼
① FIRST BREATH
  - Sensory triggers + mild hypoxia
  - -30 to -50 mmHg effort
  - Alveoli open, O₂ rises, NO released
  │
  ▼
② BLOOD FLOWS TO LUNGS
  - PVR falls <20% of foetal value
  - Pulmonary blood flow ↑↑↑
  - LA pressure rises
  │
  ├──────────────────────────────┐
  ▼                              ▼
③ FORAMEN OVALE CLOSES     Cord clamped → RA pressure falls
  (LA > RA pressure;         same pressure reversal seals the flap
  septum primum flaps shut)
  │
  ▼
④ DUCTUS ARTERIOSUS FLOW REVERSES
  (now Aorta → Pulmonary artery, briefly)
  │
  ▼
⑤ DUCTUS VENOSUS CLOSES
  (no more umbilical flow, sphincter constricts)
  │
  ▼
⑥ DUCTUS ARTERIOSUS CLOSES
  (↑O₂ + bradykinin contract the wall;
   PGE₂ falls; complete in 96 hours)
  │
  ▼
ADULT SERIAL CIRCULATION ESTABLISHED

Quick Reference - Adult Remnants