ANNALS O F C LIN IC A L A N D LABORATORY S C IE N C E , Vol. 15, No.

4
Copyright © 1985, Institute for Clinical Science, Inc.

Physiology o f the P lacen ta—

Gas Exchange
JAN M. G O PL E R U D , M .D .*
and MARIA DELIVORIA-PAPADOPOULOS, M .D .* f

Departments of *Physiology and fPediatrics,

University o f Pennsylvania School of Medicine,
Philadelphia, PA 19104

ABSTRACT

The placenta serves as the fetus’ organ of gas exchange throughout intra­
uterin e life. W hile th e dependence of fetal w ell-being on an intact m ater­
nal-placental unit has b een recognized for centuries, it is only in the last
several decades that research w ith fetal animals has begun to unravel the
m echanism s by which it regulates blood supply and oxygen, as well as its
role in th e m atern al-to -fetal tran sfer of carb o h y d rates, p ro tein s, fats,
water, and inorganic salts. The anatom y and physiology of the placenta
are p rese n ted h ere as they relate specifically to gas exchange. In addition,
co m p en sato ry ad ap tatio n s of th e fetus and p lacen ta to acute asphyxial
events will b e discussed.

Introduction ries. O nly in th e last several decades,

however, have the physiological m echa­
n ism s by w h ich th is is ac co m p lish e d
“. . . . it may be objected, That the
begun to be unravelled. As with m any
F o e tu s in th e W om b liv es, its H e a rt
advances in physiology, the u n derstand­
pulses and its Blood circulates; and yet it
ing of placental function has dep en d ed
draws in no Air, n e ith e r hath the Air any
on research w ith animal models, esp e­
access to it. To w hich I answer, That it
cially th e in tact, n o n -exteriorized fetal
doth receive Air, so m uch as is sufficient
lam b. This anim al m odel system and the
for it in its p rese n t state, from th e m ater­
introduction of radioactive m icrospheres
nal B lood by th e P la c e n ta . . . . I say
for the study of regional blood flow have
then, That th e chief use of the Circula­
b e e n key dev elo p m en ts advancing th e
tion of the Blood . . . . th ro ’ th e Placenta
u n d e rsta n d in g of placental physiology.
. . . . in an H um an Foetus, seem s to be
M o tiv a tio n to p u rsu e th is a re a of
the Im pregnation of the Blood w ith Air,
research has increased w ith the growing
for the feeding of th e Vital F la m e .”
appreciation of the placenta’s pivotal role
— J. Ray 170135
as a r b ite r o f b o th a c u te a n d c h ro n ic
The im portance of the placenta to feto- asphyxial assaults to th e feto-m aternal
m aternal gas exchange— its role for the unit.
d u ra tio n o f p re g n a n c y as th e “ fetal Historically, the consequences of p e ri­
lung”— has b e e n su sp e c te d for c e n tu ­ n a ta l asphyxia on s u b s e q u e n t h u m an
270
0091-7370/85/0700-0270 $01.50 © Institute for Clinical Science, Inc.
 PHYSIOLOGY O F PLACENTA— GAS EXCHANGE
d e v e lo p m e n t w e re firs t d e s c rib e d in
1862 by Dr. W. J. L ittle, in a p resen ta­
tion to the O bstetrical Society of L on­
don . 25 In this now classic paper, he dif­
fere n tia te s b irth in ju ry re su ltin g from
b irth asphyxia, th a t is “ in te rru p tio n of
the p roper placental relation of th e foetus
to th e m o th e r ,” from th a t r e la te d to
actual delivery, “from direct m echanical
injury to the brain and spinal co rd .” This
new and, at th e tim e, controversial dis­
tinction req u ired another h u n d red years
and experim ental verification in fetal ani­
m als b e fo re its g ra d u a l a c c e p ta n c e .
Today, perinatal asphyxia rem ains a sig­
nificant neonatal problem , accounting for
90 p e rc e n t o f c e re b ra l palsy, w ith th e
rem aining 1 0 p e rc e n t being a ttrib u ted to
postnatal factors.
Anatom y and Physiology
T he p lac e n ta physically attach es th e
fetus to the uterin e wall and is com posed
of both a m aternal (decidual) and fetal
portion (chorionic plate and villi). M ater­
nal arterial blood reaches th e placental
c o ty le d o n s th ro u g h sp ira l, te rm in a l
branches of th e u te rin e a rte rie s w hich
eject blood through arteriolar orifices in
th e decidual plate into th e intervillous
space. T his a rte ria liz e d lake o f b lo o d
then bathes th e chorionic villi projecting
into it, which contain the fetal capillaries.
Carbon dioxide and o th er w aste products
of fetal m etabolism , arriving by way of
th e u m b ilic a l a rte rie s , a re e x c h an g e d
across this intervillous space by sim ple,
passive diffusion as oxygen and nutrients
pass into the fetal circulation through the
umbilical vein from the m aternal side.
Blood in th e in te rv illo u s sp a ce d rain s
interm ittently back through th e decidual
plate, returning to the m aternal circula­
tion via the u terin e vein. Anatomically,
the hum an placenta is classified as hem -
ochorial in ty p e , 27 gas being exchanged
from m aternal red blood cells free in the
intervillous lakes, across th e chorionic
271
m em brane and fetal endothelial cell wall
to the fetal red blood cells.
U nder norm al conditions, the a rteri­
a liz ed b lo o d flo w ex itin g th e p la c e n ta
through the um bilical vein divides as it
trav erses th e liver, approxim ately h alf
p e rfu s in g th e liv e r p a re n c h y m a and
entering the inferior vena cava from the
h e p a tic v ein . T h e o th e r 50 p e rc e n t of
um bilical venous blood passes d irectly
through the ductus venosus from which
it enters the inferior vena cava and selec­
tively stream s into the right atrium and
across th e fo ra m en ovale in to th e left
h e a r t , 9 1 6 ,3 6 p ro v id in g b lo o d w ith th e
h ig h e s t oxygen s a tu ra tio n to th e fetal
brain and m yocardium .
Oxygen delivery to the fetus is a func­
tion of two variables: um bilical venous
blood oxygen concentration and um bili­
cal blood flow . 33 Since um bilical venous
blood oxygen concentration is a reflec­
tion of uterin e blood flow, factors affect­
ing it a re p rim a rily m a te rn a l, such as
hypotension, hypertension, uterin e con­
tractions, and obstruction of the m aternal
inferior v en a cava . 17 F actors adversely
affecting um bilical blood flow include
um bilical cord com pression, hem orrhage
(p la c e n ta p re v ia , a b ru p tio p lac e n ta ),
polycythem ia (excessive placental trans­
fusion), an d c a te c h o la m in e re le a s e .
Thus, the oxygen delivered to the fetus
is first d e p e n d e n t on m atern al u te rin e
blood supply, m odified by placental dif­
fusion of oxygen, and finally the product
of um bilical venous blood flow and oxy­
gen co n ten t. T he norm al oxygen p re s ­
su re v alu es in m a te rn a l an d u m b ilic a l
b lo o d v essels in h u m an s a re u te r in e
a rte ry , 80 to 100 P 0 2 m m H g; u te r in e
vein, 40 to 45; um bilical vein, 25 to 35;
and um bilical artery, 20 PO a m m H g.
Two s trik in g a sp ec ts of th is oxygen
transport cascade are the inefficiency of
sequential oxygen transfer and the low
P 0 2 e n v iro n m e n t th a t re s u lts for th e
fetus. M easurem ents in the unstressed
p re g n a n t ew e show u m b ilic a l v en o u s
272 G O PL ER U D AND DELIVORIA-PAPADOPOULOS

P 0 2 to range from 25 to 35 m m H g in the

fetal lam b, rarely exceeding 40 m m H g . 8
Fetal adaptations to this relative hypox­
em ia include th e oxyhemoglobin disso­
ciation curve of fetal blood, to be dis­
cussed later, and fetal cardiac o u tp u t,
which is high relative to th e adult.
M uch co n tro v ersy and e x p erim en tal
investigation have focused on the physi­
ology of p la c e n ta l gas e x c h an g e , th e
majority of experim ental work, by neces­
sity, being done w ith fetal animals, p ar­
tic u la rly th e feta l lam b. O f p a rtic u la r
interest have b een efforts to account for
th e d e c re a s e in oxygen te n s io n th a t
occurs across th e p la c e n ta l in te rfa c e .
E xperim ental m anipulations of u terine,
and hence fetal, oxygen supply in fetal
s h e e p 26 h av e show n th a t u m b ilic a l
venous blood oxygen tension equilibrates
with, b u t is never equal to or higher than
its d o n o r s tre a m , th e u te r in e v en o u s
blood. As se e n in fig u re 1, m a te rn a l
hyperoxia in sheep results in increm ental
elevations of u terin e venous and um bil­
ical v e n o u s oxygen te n s io n s w ith an
(A), uterine vein (V), umbilical vein (7 ), and umbilical
approxim ately 15 to 20 m m H g difference artery (a) during periods of air and oxygen inhalation
betw een the two. O ver a w ide range of in the sheep. (From Battaglia, F. C ., Meschia, G.,
low u te rin e venous blood oxygen te n ­ Makowski, E. L., and Bowes, W.: J. Clin. Invest.
47:5 4 8 -5 5 5 , 1968).
sions, th is re la tio n s h ip to u m b ilic a l
venous PO a is p reserv ed as w ell . 39 Phys­
iologically, th e n , th e ovine p la c e n ta well as the direct arteriovenous anasta-
behaves m ost like a concurrent exchan­ m oses in both the m aternal and fetal cir­
ger (figure 2 ) in w hich the m aternal to cuits of the placenta, allowing blood to
fetal blood stream s run in the same direc­ bypass areas of gas exchange. The diffu­
tion, such that the venous blood of the sion of oxygen across the placental m em ­
recipient stream equilibrates w ith that of brane may also account for some red u c ­
the donor stream . tion in umbilical venous P 0 2 com pared
A sim ila r re la tio n s h ip has b e e n to uterin e venous P 0 2. In contrast to the
reported for th e hum an placenta . 26 The lu n g , in w hich th e diffusion d ista n c e
10 to 20 m m H g oxygen m ism atch b etw een alveolus and pulm onary capil­
b e tw e en u te rin e and um bilical venous lary is 0 . 1 u, the distance from intervil­
circuits has b een a ttrib u ted to a com bi­ lous space to fetal capillary across th e pla­
nation of placental oxygen consum ption c e n ta is a p p ro x im ate ly 3 .5 u. T h e
and nonhom ogeneous placen tal p e rfu ­ placenta, however, is highly perm eable
sion. The latter relates to th e uneven and to oxygen and, in general, efficiency of
h a p h a z a rd e je c tio n of b lo o d from th e gas transfer is felt to be m ore d e p e n d en t
u te rin e a rte rie s in to th e in te rv illo u s on flo w -re la te d factors th a n on diffu-
>1
space surrounding the chorionic villi, as s io n /'
 PHYSIOLOGY O F PLACENTA— GAS EXCHANGE 273

MODELS OF PLACENTAL PER FUSIO N suited to th e in trau terin e environm ent,

A since the highest P 0 2 in um bilical vein
COUNTER CURRENT blood is about 40 m m H g. As seen in fig­
P P
u re 4, as th e oxygen te n sio n o f a d u lt
° 2 M A T E R N A L B LO O D FLO W ° 2

9 0 -4 ) ( 4— 40
blood drops from an alveolar level of 1 0 0
P L A C E N T A
m m H g to a tissue level of 40 m m H g, H b
A will unload 4.7 ml 0 2 per 100 ml blood,
9 0 — ( ) --------- 25

F E T A L B LO O D F L O W
w hereas H b F can only unload 3.0 ml 0 2
p er 1 0 0 ml blood during the sam e tra ­
A: Expected maximum p 0 2 in the fetal blood leav­ v erse . 29 In the fetus in-utero, however,
ing the placenta when flows are concurrent
across a highly permeable membrane. H b F will unload 10.3 ml 0 2 p er 100 ml
blood and H b A will unload only 8 . 8 ml
B 0 2 p e r 1 0 0 ml blood in passing from a
CONCURRENT placental PO £ of 35 m m H g to a fetal tis­
P P
° 2 M A T E R N A L B LO O D FLO W ° 2
sue PO a of 15 m m H g. These facts are
90-47 -------- ~ ( 4^ 4 0 functions purely of th e relative slopes of
P L A C E N T A
th e resp e c tiv e dissociation curves; th e
a d u lt O D C has th e g re a te r slope (and
2 5 -4 ) - ( ) — 4 0

F E T A L B LO O D F L O W
oxygen unloading advantage) at high lev­
els of oxygenation, w hereas the loading-
B: Expected p 0 2 in the presence of concurrent unloading advantage lies w ith the fetal
blood flow.
O D C at low er oxygen tensions. T hese
F ig u re 2. M odels of placental perfusion.
changes in slope, in turn, are functions

Role of F e ta l H em oglobin in Placental

Gas Exchange

Among the factors im portant for oxy­

gen transfer from m aternal-to-fetal blood
are the relative positions of the oxygen
dissociation curve (ODC) of both m other
and fetus. Prior to th e discovery of the
role of 2 ,3 -d ip h o s p h o g ly c e ra te (2 ,3 ,-
DPG) in regulating H b - 0 2 affinity, m any
in v e stig a to rs h a d n o te d d iffe re n c es
betw een “adult blood” and “fetal blood, ”
including the position of the O D C , resis­
tance to alkaline dénaturation, sedim en­
tation constants, electrophoretic m obil­
ity, absorption spectra, cyrstal form, and
amino acid com position . 1-2-3-11-22 Physio­
P0 j mmHg (pH 7.40)
logically, th e m ost im portant and fasci­
F i g u r e 3. O xyh em oglob in d issociation curve.
nating of these differences is the obser­
Curve A represents the fetal-neonatal curve, P50 =
vation that in-vivo fetal blood has higher 19 mmHg. The curve is left-shifted. Curve B rep­
oxygen affinity than adult blood, allowing resents the normal adult curve, P50 = 27 mmHg.
greater oxygenation of fetal hem oglobin Sigmoid shape is attributable to hem e-hem e inter­
action. Curves can be shifted right or left by changes
at lower P 0 2 (figure 3). in temperature, P C 0 2, pH , 2,3-D PG level, and by
The high affinity of fetal blood is well differing percentages of Hb F and Hb A.
274 G O PLER U D AND DELIVORIA-PAPADOPOULOS
Po,
o f la te ra l d isp la c e m e n ts o f th e O D C ,
w h eth er produced by pH , P C 0 2, tem ­
p eratu re, ionic surroundings of hem oglo­
bin, or its d eg ree of interaction w ith 2,3-
DPG. The latter factor is one of the most
im p o rtan t reg u lato rs of th e position of
the O D C in m aternal blood; the concen­
tration of 2,3-D PG is usually elevated in
pregnancy . 37
D espite th e advantages to the fetus of
h aving H b F , s u b s titu tio n o f “ a d u lt”
erythrocytes in the fetus by intrauterine
transfusion (as for Rh-isoim munization),
shifts th e fetal O D C to the right. This
procedure, however, does not as a rule
result in undergrow n, stillborn, or oth­
erwise im paired neonates, showing that
the fetal O D C is not essential for fetal
w ell b e in g . 30 E x p e rim e n ta lly in d u c e d
increases in affinity of m aternal hem oglo­
bin in the preg n an t rat result in sm aller
fetuses at term , b u t lim ited experience
in the hum an species suggests no such
adverse effect . 18’31
F ig u re 4. Oxygen load­
ing and unloading capaci­
tie s o f ad u lt and fetal
blood at various oxygen
tensions. See text for fur­
th er explanation. (From
Nelson, N. M. in Smith,
C. A. and N elson, N. M .,
P h y sio lo g y o f th e N e w ­
born Infant, 1976.)
W h en fetal grow th is sev erely com ­
p ro m is e d by p la c e n ta l insufficiency,
increased H b F synthesis results . 6 P re ­
m ature infants have higher H b - 0 2 affin­
ity, se c o n d a ry to lo w e r 2 ,3 -D P G and
increased percentage of H b F. The fetus
responds to m aternal cigarette smoking
by decreasing its P50 in relationship to
the increase in m aternal carboxyhemo-
globin . 12 This change in P50 is due to
statistically significant increase in H b F
synthesis, which is, however, biologically
incapable of com pensating for changes in
oxygen transport secondary to m aternal
sm oking . 12
The transition in-utero from predom i­
nantly (90 to 95 percent) H b F synthesis
to H b A synthesis occurs at 30 wks, and
is not altered by the birth process. P re­
m aturely born infants follow the in-utero
tra n s itio n . 5 H e m o g lo b in F sy n th e sis
declines rapidly in term infants postna-
tally until it is negligible at 16 to 2 0 wks
of age . 7
 PHYSIOLOGY O F PLACENTA— GAS EXCHANGE
F etal R esponse to Acute
Asphyxia E vents
Asphyxia occurs w hen tissue m etabo­
lism c o n tin u e s in th e a b s e n c e of a d e ­
q u a te oxygen supply. I n tr a u te r in e
asphyxia, specifically th e failure of th e
p la c e n ta to p ro v id e a d e q u a te gas ex­
change for th e fetus, is expressed clini­
cally as fetal hypoxia, hypercarbia, and
acidosis associated w ith late d e c e le ra ­
tions of th e fetal h eart rate and/or passage
of m econium . G iven th e anatom ical and
physiological a rra n g e m e n t o f th e fetal-
placental u nit described in th e previous
section, w hat capacity does the system
have to adjust to alterations in oxygen
supply. This section will discuss com pen­
satory m echanism s invoked during acute
asphyxial events. Again, as w ith experi­
m ents determ ining th e norm al state, the
data presen ted are prim arily from studies
of fetal animals, especially th e fetal lamb.
T he m ost extensive stu d ies of acute
deprivation of fetal oxygen supply have
involved re d u c e d m a te rn a l a rterial 0 2
content . 15 Fetal hypoxem ia induced by
m aternal b re a th in g of re d u c e d oxygen
concentrations resu lted in increased fetal
arterial p re ssu re , d e c re a se d fetal h e a rt
rate, and only a m inim al decrease in fetal
cardiac output. T here was also a signifi­
cant redistribution of fetal cardiac out­
put, w ith an increase in blood flow to the
fetal heart, brain, and adrenals, accom­
panied by a reduction in flow to the gut,
kid n ey s, sp le e n , c arcass, a n d lungs.
W h en fetal lam bs w e re a c id e m ic as
w ell as h y p o x em ic, th e s e c irc u la to ry
re sp o n se s w e re e v e n m o re d ra m a tic ,
with greater increases in fetal brain, car­
diac, and adrenal flow w hile flow to the
rest of th e body decreased. In addition,
fetal cardiac o u tp u t was d im in ish e d in
the hypoxem ic-acidem ic lam bs and the
percent distribution of cardiac output to
the placenta increased.
S evere partial asphyxia secondary to
275
um bilical cord com pression , 21 to a pH of
7.04 and an 0 2 saturation of 19 p ercen t
from 50 p ercen t in fetal lambs, produced
the expected increase in cerebral blood
flow to all regions of the brain, w ith larg­
est increases to the brain stem and deep
cerebral structures. Fetal arterial blood
pressure rose during asphyxia and cor­
re la te d clo sely w ith reg io n a l c e re b ra l
blood flow increases, suggesting that it
may be a critical factor in determ ining
cerebral blood flow. T he redistribution
of blood flow to the fetal brain during
asphyxia is a potentially reversible p h e ­
nom enon. Fetal lam bs subjected to a 90
m inute period of hypoxia (POa 12 to 15
mmHg) w ere studied 4, 24, and 48 hours
after hypoxia . 4 Regional cerebral blood
flows, which rose an average of 95.9 p e r­
cent com pared to control during th e hyp­
oxia, had retu rn ed to pre-hypoxia levels
by four hours and rem ained stable at 24
and 48 hours post-hypoxia, showing no
evidence of post-ischem ic hypoperfusion
syndrom e. O th e r organ blood flows also
retu rn ed to near baseline levels by four
hours post-hypoxia.
F etal oxygen supply is a function of
um bilical blood flow as well as um bilical
venous oxygen content, but, as discussed
e a rlie r, fe to -m a te rn a l gas e x c h an g e is
particularly vulnerable to alterations in
flow . 27 Cineangiographic studies of the
R hesus m o n k ey p la c e n ta , 34 w h ich is
hem ochorial and th ere fo re stru c tu ra lly
sim ilar to th e h u m a n p la c e n ta , h av e
d e m o n s tra te d re d u c e d flow th ro u g h
e n d o m e tria l sp iral a rte ria ls in to th e
intervillous spaces d u ring u te rin e con­
tractions. L ater studies using radioactive
m icrospheres , 24 also in pregnant Rhesus
m onkeys near term , have m ore quanti­
tatively docum ented the effects o f labor
on u te r in e an d , especially, p la c e n ta l
blood flow. C om pared to baseline levels
p rio r to labor, th e p la c e n ta re c e iv e d
m arkedly different flow during contrac­
tions ( —64 p e rc e n t) th an d u rin g th e
276 G O PLER U D AND DELIVORIA-PAPADOPOULOS
relaxation p h ase b e tw e e n contractions
( + 60 percent). These alternating periods
of placental ischemia and reactive hyper­
em ia may balance each o th er w hen con­
tra c tio n s a re re g u la r a n d w ell sp aced .
H ow ever, w h e n c o n tra c tio n s b e c o m e
m ore freq u en t and vigorous, as happens
in later states of hum an labor, or w hen
tetanic contractions occur as a result of
excessive oxytocin infusion, this balance
may be altered, resulting in fetal hypox­
em ia and/or acidem ia as ev id e n c e d by
decelerations of fetal heart rate.
Umbilical blood flow has b een shown
to rem ain constant despite acute changes
in fetal blood oxygen concentrations over
a w ide range of v a lu e s . 1 5 1 7 ,3 3 F u r th e r ­
m ore, alterations in m aternal system ic or
u te rin e circulations (increased venous
pressure or decreased arterial pressure)
have no direct effect on um bilical blood
flow . 10,38 A variable and delayed fall in
um bilical blood flow is o b serv ed once
fetal hypoxem ia and bradycardia occur,
b u t this resp o n se was abolished w hen
atropine was given to prev en t the bra­
dycardia of fetal hypoxemia. Elevations
of umbilical venous pressure or reduc­
tion of um bilical arterial pressure, how ­
ever, do effect u m b ilic a l b lo o d flow
in stantaneously a n d reproducibly. This
resultant fall in um bilical flow could not
be abolished by atropine, suggesting that
fetal b ra d y c a rd ia — p re v e n te d by a tro ­
p in e — was not responsible for the um bil­
ical flow decrease.
A nother im portant elem en t in the fetal
response to asphyxiai stress is decreased
heart rate, especially w ith the expanded
role of fetal h eart rate m onitoring cur­
rently in clinical obstetrics. The prim ary
trigger of fetal bradycardia is hypoxemia.
Studies w ith fetal sh eep 19,28,32 have dem ­
onstrated a chem oreceptor response to
h y poxem ia th a t stim u la te s th e vagus
n e rv e , w h ich in tu r n m e d ia te s th e
decrease in fetal h e a rt rate. The response
can be abolished by B -adrenergic block­
ade w ith atropine. The degree of fetal
bradycardia appears to be a function of
fetal P a 0 2, 19,28 b u t first requires P a 0 2 to
fall below a critical threshold level.
In the fetal lam b, this critical PaOz has
b e e n id e n tifie d as a p p ro x im ate ly 16
m m H g , 19 while in the hum an fetus it is
19 m m H g . 13 Fetal heart rate, then, does
not fall in response to hypoxem ia until
th e critical P a 0 2 level has been reached.
These sam e studies have shown that tis­
sue hypoxia is n ot necessarily p re s e n t
w hen fetal bradycardia occurs, implying
that tissue 0 2 dem ands can still be m et
in th e presence of significant fetal hypox­
emia. Clinically, this would explain why
fe ta l h e a rt ra te re d u c tio n s in h u m an
fetuses, so-called late decelerations, are
not necessarily associated with evidence
of hypoxia at b irth , 14,23 as reflected by
acidem ia or low Apgar scores (an assess­
m e n t scale based on h e a rt rate, color,
tone, respiratory effort, and reflex, used
in th e delivery room to evaluate a new ­
born at one and five m inutes). Fetal lam b
s tu d ie s 39 d e m o n s tra te th e c ap acity o f
th e fetus to w ith sta n d a 40 to 50 p e r ­
c e n t re d u c tio n in 0 2 deliv ery d u rin g
d e c re a sed u te rin e blood flow , w ith o u t
affecting fetal O z consum ption. O ne fac­
tor in this rem arkable adaptability is the
relatively high percentage of total fetal
oxygen re q u ir e m e n t d e s ig n a te d for
g ro w th u n d e r ste a d y -sta te c o n d itio n s,
w hich can be elim inated during tim es of
stress. A nother potential com pensatory
m echanism for reduced 0 2 delivery is an
increase in fetal 0 2 extraction at the tis­
sue level.
T h e m ech an ism s by w hich fetal r e ­
sponses to hypoxic stress are regulated
a re only b e g in n in g to b e u n d e rs to o d .
A rg in in e v a so p re ssin is o n e c h e m ica l
m e d ia to r th a t ap p e ars to h av e a role.
Infused intravenously in fetal sheep 20 to
achieve serum levels actually seen w ith
feta l h y poxia, a rg in in e v a so p re ssin
resu lted in characteristic redistribution
 PHYSIOLOGY O F PLACENTA— GAS EXCHANGE
of fetal blood flow w ith increases to m yo­
cardial, cerebral, and um bilical-placental
c irc u its. T h e re was also a d e c re a s e in
fetal h e a rt ra te a n d in c re a s e in b lo o d
pressure w ith little change in com bined
ventricular output. W hile these findings
suggest th at vasopressin may contribute
to the fetal response to acute hypoxemia,
o th e r a sso c ia te d c irc u la to ry ch an g es,
such as d e c re a s e d a d re n a l, re n a l, and
pulm onary blood flow, did not occur in
response to vasopressin alone, favoring
a m ulti-factor triggering response m ech­
anism . C atecholam ines and p ro stag lan ­
dins may prove im portant in this regard,
and c e rta in ly feta l b a ro re c e p to rs and
c h em o recep to rs also p a rtic ip a te in th e
fetal response to acute asphyxia.
Sum m ary
T he p la c e n ta is a h ig h ly sp e c ia liz e d
organ that forms th e critical link betw een
m aternal and fetal circulations through­
out gestation. W hile gas exchange is b ut
one o f its fu n c tio n s, it is u n iq u e ly
a d a p te d for th is ro le in m any w ays.
M aternal and fetal vasculature intersect
in such a way (concurrent exchanger) that
u m b ilical v e n o u s b lo o d , th e “ a rte ria l-
ized” fetal stream , equilibrates w ith u te r­
ine v en o u s b lo o d , p ro v id in g a sta b le
although relativ ely hypoxem ic e n v iro n ­
m ent for th e fetus. T he fetus, in turn,
has a d a p te d to th is oxygen tra n s fe r
schem e w ith its unique oxygen dissocia­
tion curve and high cardiac output. In
addition, th e fetus is capable of respond­
ing to both acute and chronic depriva­
tions of oxygen supply from the placenta.
Acutely, fetal hypoxia results reversibly
in decreased h e a rt rate and red istrib u ­
tion of fetal blood flow to favor cerebral,
m y o card ial, a n d a d re n a l flow . Less
severe but m ore steady-state hypoxemia,
as seen w ith m aternal cigarette smoking,
or placental insufficiency, com prom ises
fetal grow th capacity and increases H b F
production. The c u rre n t challenge to pla­
277
cental physiologists is further delineation
o f b o th th e c h e m ica l and s tru c tu ra l
m ediators of m aternal-fetal interaction.
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