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# Placental exchange: oxygen, carbon dioxide, nutrients and drugs

- Mechanism
- Exam priority: medium

The fetus gets oxygen at low pressure because its hemoglobin grabs O₂ more tightly; most small, fat-soluble molecules cross the placenta.

Updated Nov 13, 2026

Also called: Double Bohr effect, Transplacental transfer

## Key points

- Umbilical vein (O₂-richest fetal blood) has PO₂ ≈ 30 mmHg, yet saturation ≈ 80% thanks to HbF.
- HbF (α₂γ₂) binds 2,3-BPG poorly, so its P₅₀ is ≈ 19 mmHg versus ≈ 27 mmHg for adult HbA: the fetal curve is shifted left.
- Double Bohr effect: fetal blood gives up CO₂ (pH rises, affinity rises) while maternal blood takes CO₂ up (pH falls, affinity falls), both favouring O₂ transfer.
- CO₂ crosses easily; maternal hyperventilation in pregnancy (PaCO₂ ≈ 30 mmHg) widens the fetal-to-maternal CO₂ gradient.
- IgG crosses actively through the neonatal Fc receptor (FcRn), mostly in the third trimester; IgM does not cross.
- Small, lipid-soluble, un-ionized, unbound molecules cross best; large or highly charged molecules such as heparin and insulin barely cross.

## What it is

Maternal blood fills the intervillous space and bathes fetal villi; the two circulations never mix. Gases cross by diffusion, so exchange depends on the partial pressure gradient, the surface area and the thinness of the barrier, which all grow with gestation. The fetus lives at a PO₂ that would be dangerously low for an adult, and compensates with high-affinity fetal hemoglobin, a high hemoglobin concentration and the double Bohr effect.

## How it works, step by step

- Maternal spiral arteries spurt blood into the intervillous space; it flows over the villi and drains into uterine veins.
- O₂ diffuses from maternal blood (PO₂ in the space ≈ 40–50 mmHg) into fetal capillaries, down a gradient of about 20 mmHg.
- Fetal blood loads O₂ at low PO₂ because HbF has high affinity and fetal hemoglobin concentration is high (≈ 15–17 g/dL).
- At the same time fetal CO₂ diffuses to the mother: fetal blood turns more alkaline (more O₂ affinity), maternal blood more acidic (less O₂ affinity).
- Glucose crosses by facilitated diffusion (GLUT1), so fetal glucose runs below maternal and follows it.
- Amino acids, calcium and iron are actively transported, so fetal levels are higher than maternal levels.
- Free fatty acids, water and electrolytes cross by diffusion or carriers; IgG crosses by FcRn-mediated transcytosis.
- Exchange is mostly flow-limited: low uteroplacental flow (preeclampsia, hypotension, strong contractions) cuts O₂ supply first.

### Oxygen–hemoglobin dissociation curve

**P50** 19.0 mmHg **Arterial blood** 99 % **Mixed venous blood** 88 % **O₂ given up to the tissues** 11 %

HbF binds little 2,3-BPG: its P50 is lower, so it takes O₂ from maternal blood in the placenta.

Left shift (P50 19.0 mmHg): Hb holds O₂ more tightly and gives up less in the tissues.

- Current curve
- Normal curve (pH 7.40 · 37 °C)
- Arterial blood (PO₂ 100)
- Mixed venous blood (PO₂ 40)
- O₂ given up to the tissues

Compare HbF with HbA: the fetal curve sits to the left, so fetal blood loads O₂ at the low PO₂ of the placenta.

## Typical values near term (illustrative)

| Parameter | Value | Note |
| --- | --- | --- |
| PO₂ maternal artery | ≈ 95–100 mmHg | |
| PO₂ in intervillous space | ≈ 40–50 mmHg | |
| PO₂ umbilical vein | ≈ 30 mmHg | best-oxygenated fetal blood |
| PO₂ umbilical arteries | ≈ 15–20 mmHg | |
| P₅₀ HbF / HbA | ≈ 19 / 27 mmHg | |
| Maternal PaCO₂ in pregnancy | ≈ 28–32 mmHg | |
| Uteroplacental blood flow at term | ≈ 500–750 mL/min | ≈ 10–15% of maternal cardiac output |

Approximate values for a healthy adult at rest; each laboratory sets its own ranges.

## How different substances cross the placenta

| Substance | Route | Fetal vs maternal level |
| --- | --- | --- |
| O₂, CO₂ | Simple diffusion | Fetal PO₂ lower, PCO₂ slightly higher |
| Glucose | Facilitated diffusion (GLUT1) | Lower than maternal |
| Amino acids, Ca²⁺, phosphate, iron | Active transport | Higher than maternal |
| IgG | FcRn transcytosis | Can exceed maternal at term |
| IgM, large proteins, heparin, insulin | Barely cross | Very low |
| Lipid-soluble small drugs, alcohol, nicotine | Diffusion | Near maternal |

## Clinical notes

- Weak bases such as local anesthetics can be trapped in the slightly more acidic fetal blood (ion trapping), especially if the fetus is acidotic.
- Maternal anti-D IgG crosses the placenta and attacks RhD-positive fetal red cells (hemolytic disease of the fetus and newborn).
- Placental insufficiency limits O₂ and nutrient supply and leads to fetal growth restriction; the fetus redistributes flow to the brain (brain sparing).
- Maternal carbon monoxide from smoking binds HbF tightly and lowers fetal O₂ delivery.

## Memory aid

The fetus is the 'greedy sponge': it soaks up O₂ (left-shifted HbF) and squeezes out CO₂, which makes it greedier still.

## Test yourself

Think of the answer, then tap the question to see it.

## Why can fetal blood reach about 80% saturation at a PO₂ of only 30 mmHg?

HbF binds 2,3-BPG poorly, so it has higher O₂ affinity (P₅₀ ≈ 19 mmHg); the double Bohr effect at the placenta raises fetal affinity further.

## What is the double Bohr effect?

As fetal blood gives CO₂ to the mother its pH rises and O₂ affinity increases, while maternal blood receiving CO₂ becomes more acidic and releases O₂ more easily.

## A newborn has a positive antibody test against an infection the mother had. Which antibody class can explain this without fetal infection?

IgG, which crosses the placenta through FcRn; IgM does not cross, so fetal IgM suggests infection of the fetus itself.

## Which drug features favour transfer across the placenta?

Low molecular weight, high lipid solubility, low ionization at physiological pH and low protein binding. Large, charged molecules such as heparin cross poorly.

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## Connections

## Related topics 3

- [The placenta and pregnancy hormones](https://durgical.com/en/physiology/the-placenta-and-pregnancy-hormones/)
- [Fetal circulation and the transition at birth](https://durgical.com/en/physiology/fetal-circulation-and-the-transition-at-birth/)
- [Oxygen transport and the dissociation curve](https://durgical.com/en/physiology/oxygen-transport-and-the-dissociation-curve/)

## Related conditions 2

- [Fetal growth restriction](https://durgical.com/en/conditions/fetal-growth-restriction/)
- [Rh alloimmunisation in pregnancy](https://durgical.com/en/conditions/rh-alloimmunisation-in-pregnancy/)

## In Biochemistry 2

- [Hemoglobin variants (HbA, HbA2, HbF, HbS, HbC)](https://durgical.com/en/biochemistry/topics/hemoglobin-variants/)
- [Oxygen binding: haemoglobin versus myoglobin](https://durgical.com/en/biochemistry/topics/oxygen-binding-haemoglobin-versus-myoglobin/)

[← All of physiology](https://durgical.com/en/physiology/)

Educational physiology content; not a diagnostic or treatment guide and no substitute for a health professional's advice. Values are approximate references. No doses are given.

Sources: [Physiology, Placenta](https://www.ncbi.nlm.nih.gov/books/NBK538332/) (StatPearls (NCBI Bookshelf), 2023); [Embryology, Placenta](https://www.ncbi.nlm.nih.gov/books/NBK551634/) (StatPearls (NCBI Bookshelf), 2023).

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Representative model, for educational purposes only.

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