Download Hypothesis 1

Physiological Problems of the
Fetus and Placenta
Immune Attack
• Why isn’t the fetus rejected by the mother’s immune
system?
• Hypothesis 1: uterus is a special immunologically safe
place. But, ectopic pregnancies can occur and succeed.
• Hypothesis 2: the placenta is able to protect the fetus
from antibody-mediated attack by restricting passage of
fetal antigens into the mother’s body and maternal
antibodies into the fetal circulation. Yes, but how about
Rh disease, in which Rh- mother can develop antibodies
to Rh+ fetus and cause miscarriage?
• With contemporary methods, it has been shown that
mothers are invaded by small numbers of fetal cells in
each pregnancy and these cells may survive in mother’s
body for extended periods. Consequences – bad:
autoimmune disease – good: mother makes a better
tissue donor for her children.
Gas Exchange Between Mother and Fetus
• Oxygen: PO2 of maternal blood in placental blood sinuses is about
30-35 mmHg. PO2 of fetal blood in umbilical vein is about 30 mmHg.
So, fetal blood must load O2 at a considerably lower PO2 and with a
considerably smaller gradient than adult blood.
• A partial solution is provided by fetal Hb, which consists of 2 α
chains and 2 γ chains rather than 2 α chains and 2 β chains, and is
left-shifted relative to adult Hb. This gives about 85% saturation for
blood in the umbilical vein. Also, the fetal blood has an O2 carrying
capacity about 50% higher than maternal blood.
• CO2: the gradient between maternal and fetal blood is only 5 mmHg,
so CO2 transport is about half as efficient as in the adult lung.
• This crummy situation is the result of the truly goofy design of
the reproductive physiology of placental mammals.
Roadmap of fetal-placental circulation
Umbilical vein
(80% sat)
Placenta
Umbilical
arteries
(58% sat)
Ductus venosus
Fetal Body
Left Heart
Ductus
arteriosus
Green connections will
be eliminated at birth
Lower body venous
blood (27% sat)
Vena cava
(67% sat)
Lungs
Right Heart
Foramen ovale
Placental venous
blood joins the
fetal circulation via
the ductus
venosus in the liver
The numbers show the
percentage of fetal cardiac output
that passes each checkpoint.
Note that about half of the fetus’
cardiac output goes to the fetal
body and the other half to the
placenta. At the junction of
ductus venosus and inferior vena
cava, venous blood from the fetal
body mixes with relatively
oxygenated umbilical cord blood.
Two
anatomical
shunts – the
ductus
arteriosus and
the foramen
ovale - allow
most of the
right heart’s
output to
bypass the
pulmonary
loop
Summary of blood oxygenation levels in the
fetal circulation
• Lungs are collapsed, so pulmonary loop R is
high; with placenta in place and little sympathetic
outflow, systemic loop R is low.
• A R to L shunt operates via ductus arteriosus
and foramen ovale
• Fetal vena cava blood is a mixture of 80%
saturated blood from placenta and 27%
saturated blood from fetal lower body, so when
the two bloods mix at the right atrium, the Hb
saturation is about 67%.
• About ½ of fetal cardiac output flows to the
placenta.
Circulatory Changes at Birth
• Lungs inflate: ventilation stimulated by cold, asphyxia;
pulmonary arterioles dilate, pulmonary resistance falls
• Systemic loop resistance rises: large sympathetic
outflow during birth, removal of placenta
• Foramen ovale closes: swinging door effect
• Ductus venosus closes: ?
• Ductus arteriosus closes: prostaglandin involved
• Umbilical vessels close: probably several factors
involved. Note that the umbilical vein is still available for
intravenous drug delivery in adults.
What would the
consequences
be if one of
these events
didn’t happen?
Birth Stresses and Responses in the
Neonate
• What are the stresses?
– Hypoxia
– Need to start thermoregulating
– Need to inflate lungs and start breathing
– Pressure – especially on the head during
vaginal birth
Central Role of Adrenal Catecholamines
• Large surge of catecholamine is released during
birth – levels in blood can reach 50 nM – about
6X higher than in exercising adults. If asphyxia
occurs, the concentration can reach 200 nM.
• Effects:
– Breathing: dilates bronchioles, increases pulmonary
surfactant secretion, promotes fluid absorption
– Vascular: peripheral vasoconstriction; MAP
increases; increased pressure in systemic loop closes
foramen ovale.
– Metabolic: mobilizes glucose; stimulates heat
production by brown fat
– CNS: promotes alertness
Brown fat provides heat for the brain and
thorax for several months after birth
• Unlike white fat, brown fat contains a high density of
mitochondria
• An uncoupling factor (a H+ channel) is expressed in
response to T3
• The uncoupling factor is activated in response to
epinephrine
• Uncoupled mitochondria convert almost all of the energy
of fat catabolism to heat rather than phosphorylation
potential.
• True hibernators retain brown fat for rewarming in the
spring
• We now know that adult humans have some brown fat
Vaginal birth is usually better
• Caesarian-delivered babies don’t get the
beneficial effects of sympathetic activation
• Caesarian rate is 15-20% of deliveries – roughly
50% of unplanned Caesareans seem to be
unnecessary
• In evaluating the extent of fetal distress in a
difficult labor, it is best to measure the pH of
scalp blood (<7.25 indicates asphxia), rather
than make decision on basis of fetal heart
monitor.