38. Placental Transfer Flashcards
What are the main functions of the placenta?
1
> Gas exchange
2
> Nutrient and waste exchange
3
> Transfer of immune complexes
4 > Hormone synthesis, e.g. HCG, oestrogens, progesterone, TSH, prostaglandins.
Describe the mechanisms by which substances are
transferred across the placenta
Placental transfer is subject to exactly the
same rules governing transfer
of substances across
all semi-permeable phospholipid membranes.
Mechanisms of transfer include:
1
> Simple diffusion, e.g. O2 and CO2
2
> Facilitated transport, e.g. glucose
3
> Secondary active transport, e.g. amino acids
4
> Active transport, e.g. iron and calcium
5
> Pinocytosis, e.g. IgG
6
> Bulk transport.
What factors affect the transfer of substances across the
placenta?
All substances present in the
maternal circulation are
potentially available to the fetus.
The following factors govern
transfer across the placenta.
1 > Lipid solubility: The more lipid-soluble a substance is , the more readily it will diffuse across a lipid membrane, and so the placenta.
2 > Degree of ionisation: The more ionised a substance is, the less easily it diffuses across the placenta.
3 > Degree of protein binding: Only the unbound (‘free’) substance is available to cross any membrane, and so a highly bound substance will not cross the placenta readily. Pregnant women have relatively lower total protein contents of their blood and so theoretically a higher free fraction of a given substance might be present.
4
> pH: This affects the degree of
ionisation of the drug,
as dictated by its pKa.
Also, acidosis decreases protein binding.
5
> Molecular weight:
Substances with a molecular weight <600 Daltons
cross readily.
6
> Concentration gradient across the placenta: This affects speed of transfer
Local anaesthetics are often
used during labour
. Describe the
transfer of local anaesthetics
from the mother to the fetus.
> Bupivacaine
is the most commonly used local anaesthetic,
given either as epidural or subarachnoid injection.
It is used because it has fewer motor
effects than other
drugs available and has a
relatively long duration of action.
> It can cross the placenta,
but less readily than lignocaine
because its pKa is higher than lignocaine’s,
making it more ionised at physiological pH.
> The fetus has a lower pH than its mother,
and so there is a risk of
‘ion trapping’,
where the drug
crosses into the fetus,
becomes more ionised,
and therefore cannot move out again.
effect is exacerbated if the
fetus becomes more acidotic,
risking local anaesthetic toxicity
Describe the transfer of
pethidine.
> Pethidine is the most commonly used
opioid for labour pain and
can be prescribed by the midwives
in most UK maternity units.
> It is a highly lipid-soluble drug
and so it
passes freely across the placenta
reaching equilibrium in about 6 minutes
and reaching maximum levels in
the fetus at around 2–3 hours.
> It is metabolised to norpethidine,
which is less lipid soluble and therefore
remains in the fetus much longer.
> Norpethidine has little analgesic value
and causes sedation and
respiratory depression
and is pro-convulsant.
Its half-life in the mother is
up to around 20 hours,
but in the neonate can be as much as 62 hours.
Describe the Bohr effect
in relation to placental gas
exchange.
Consider drawing the oxyhaemoglobin
dissociation curve and using it to illustrate your answer.
> The Bohr effect describes the movement
to the left or right of the oxyhaemoglobin dissociation curve,
depending on the
surrounding CO2 tension
and the resulting pH.
> Ambient CO2 diffuses into
red blood cells and
dissociates to form
H+ and HCO3-
This causes the curve to shift to the right,
as there is a reduction in the affinity of
haemoglobin for oxygen.
This encourages offloading of oxygen to the tissues.
This mechanism is important in the
utero-placental circulation.
As the mother’s blood flows through the
uterus it is exposed to the high CO2
tensions generated by the fetus excreting CO2.
The CO2 diffuses into
the mother’s red blood cells
and dissociates as described.
As the fetus offloads its CO2 to its mother,
who ‘accepts’ it,
the fetus’ curve moves left, while the maternal one moves right.
This is called the ‘double Bohr effect’.
> The fetal haemoglobin has a P50 of ~2.5 kPa and so lies to the left of the mother’s whose P50 is ~3.5 kPa.
This supports uptake of oxygen by the
fetus.
How is the Haldane effect
relevant to the placenta?
The Haldane effect describes the
increased affinity of
deoxygenated haemoglobin
for CO2 and vice versa.
This is relevant across the placenta
because as the fetus gives up
CO2 it increases its affinity for O2,
and as the mother gives up her
O2 her haemoglobin has an
increased affinity
for the CO2.
= the ‘double Haldane effect’.
Describe the placental handling
of the following anaesthetic
drugs.
> Thiopentone:
Suxamethonium:
ndmr
Ephedrine
> Thiopentone:
Crosses the placenta rapidly but
the neonate does not suffer
excessive sedation unless doses exceed 8 mg/kg.
Suxamethonium:
Does not cross the placenta in significant quantities unless the mother suffers from pseudocholinesterase deficiency, allowing significant concentrations to be present in her blood for a prolonged amount of time.
The normally decreased levels of pseudocholinesterase found in pregnancy are not clinically significant.
> N on-depolarising neuromuscular blockers:
These fully ionised, bulky,
poorly lipid-soluble drugs
do not cross the placenta.
Ephedrine: Crosses easily.
