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HEPATOLOGY Vol. 3, No.2, pp. 254-258, 1983
Copyright 01983 by the American Association for the Study of Liver Diseases Printed in U S A .

Seecial Articles
Hepatic and Ductus Venosus Blood Flows
During Fetal Life
M. RUDOLPH
ABRAHAM
Departments of Pediatrics, Physiology, and Obstetrics, Gynecology, and Reproductive
Sciences, Cardiovascular Research Institute, University of California, San Francisco,
California 94143
The course of the venous circulation in the fetal liver has been studied in fetal lambs by means of
the radionuclide-labeled microsphere technique. About 50% of umbilical venous blood passes
through the ductus venosus, while the remainder is distributed to both lobes of the liver. Portal
venous blood is largely distributed to the right lobe of the liver, with a small proportion passing
through the ductus venosus and none to the left lobe. Because of these flow patterns, oxygen
saturation is lower in the right than in the left hepatic vein. Left hepatic venous blood joins the
ductus venosus stream and these preferentially pass through the foramen ovale, whereas right
hepatic venous blood joins the distal inferior vena caval stream and preferentially passes through
the tricuspid valve. These patterns favor distribution of well-oxygenated blood to the fetal heart
and brain. Hypoxia and reduced umbilical venous return are associated with reduced flow through
the hepatic microcirculation with proportionately greater ductus venosus flow. In the fetus, the
liver has a major role in influencing venous return to the heart and in regulating distribution of
oxygen and energy substrate supply to different fetal organs.

Blood flow to the liver in the adult is provided from
the hepatic artery and the portal vein. Total liver blood
flow has been calculated to be about 100 to 130 ml per
100 gm per min, and about 25 to 30% of flow is derived
from the hepatic artery (1).The blood flow to the liver
represents about 25% of cardiac output, and thus the
liver contributes one-quarter of total venous return to
the heart. Also, the liver may be of considerable impor-
tance in regulating blood volume. It is estimated that
about 25% of liver volume is occupied by blood, and this
accounts for about 10%of total blood volume.
During fetal life, the liver receives its blood flow from
three sources: the hepatic artery, the portal vein, and the
umbilical vein. The hepatic artery provides separate
branches to the liver substance, as in the adult, but the
portal and umbilical veins join in the portal sinus. There
is often a misconception of the morphological arrange-
ment of these vessels in the sinus; it is often presented as
a confluens, from which right and left portal veins and
the ductus venosus arise. However, it was pointed out by
Lind (2) and Barry (3) in studies in the human fetus, that
portal branches to the left lobe of the liver arise directly
from the umbilical vein; the ductus venosus then arises,
and the umbilical vein then arches to the right lobe,
where it is joined by the portal vein. The portal venous
This work was supported by a grant from the USPHS (Program
Project HL 24056).
Address reprint requests to: Abraham M. Rudolph, M.D., 1403-HSE,
University of California, San Francisco, California 94143.
254
branches to the right lobe are given off beyond the
junction of the portal and umbilical veins. This same
arrangement is present in the fetal lamb (4,5).A silicone
rubber cast demonstrating the venous anatomy of the
liver is shown in Figure 1.
DUCTUS VENOSUS BLOOD FLOW
The ductus venosus has been considered to serve as a
bypass of the hepatic microcirculation for umbilical and
portal venous blood. However, because of its location
within the liver substance, little is known about its actual
functional role. If this vessel was reactive, it could have
a major role in regulating the proportions of umbilical
and portal venous blood that pass through the fetal liver
substance. A sphincter has been described in the ductus
venosus at its origin from the umbilical vein, both in the
sheep (Barron, B. Anatomical Record 1942; 82:398, Ab-
stract) and in the human (6), but could not be demon-
strated by others (3, 7). In the silicone cast shown in
Figure 1, a ring of constriction, suggesting the presence
of a sphincter, is noted at the origin of the ductus venosus.
Using angiographic techniques, it was suggested that the
ductus venosus may be influenced by vasoactive sub-
stances such as norepinephrine (a), but it is difficult to
evaluate this information because the diameter of the
ductus venosus could have been altered passively by
changes of intravascular pressure and blood flow. In a
recent review of the ductus venosus, Edelstone suggested
that the ductus venosus responds passively to changes of

Vol. 3, No. 2, 1983 HEPATIC AND DUCTUS VENOSUS BLOOD FLOWS DURING FETAL LIFE
FIG. 1. Silicone rubber cast of major venous channels in fetal liver,
as seen from the left side. The umbilical vein (UV) provides branches
to the left lobe (LP) and then divides into the ductus venosus (DV) and
the arch which joins the portal vein (PV). Branches are then given to
the right lobe (RP).The left hepatic vein (LHV) is seen to join the
ductus venoms before connecting with the inferior vena cava (IVC).
The right hepatic vein (RHV) joins the inferior vena cava separately.
A small caudate lobe vein (CV) enters the inferior vena cava directly.
A constriction, suggesting a sphincter, is noted a t the junction of the
ductus venosus with the major umbilical vein [from Bristow et al.
(31.
pressure, and that it possesses little active vasoregulation
(9).
We have applied the radioactive-labeled microsphere
method to studying the relative proportions of umbilical
venous return passing through the liver and the ductus
venosus. When these 15-pm diameter plastic spheres are
injected into the umbilical venous circulation, those that
enter the hepatic microcirculation are trapped in the
liver. The spheres that pass through the ductus venosus
are distributed to the rest of the fetal body and to the
placenta; they are trapped in these circulations and there
is negligible recirculation. In the fetus, the presence of
the foramen ovale and ductus arteriosus allows spheres
to cross to the left side of the heart and to the systemic
arterial circulation. A certain number of the spheres
entering the descending aorta will be distributed to the
liver through the hepatic arteries, but, as discussed below,
this represents a very small amount of the total injected.
The proportion of umbilical venous blood passing
through the ductus venosus thus can be calculated by
the percentage of total microspheres injected that appear
in the fetal body and placenta.
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255
In addition to measuring the proportion of umbilical
venous blood passing to the liver and through the ductus
venosus, it is possible to calculate the proportions of
umbilical venous blood distributed to each fetal organ
and to the placenta. If a reference sample of blood is
withdrawn from a carotid arterial and femoral arterial
catheter simultaneous with the injection of the micro-
spheres, the actual blood flow to each organ can be
calculated by relating the radioactivity in the reference
sample to the radioactivity in each upper or lower body
organ. By using microspheres with different radionuclide
labels, several measurements can be made in the same
fetus during various experimental manipulations. We
have described the use of the radionuclide-labeled micro-
sphere method for studying the fetal circulation previ-
ously ( 10- 12).
Using the microsphere technique, we have shown that
the proportion of umbilical venous blood flowing through
the ductus venosus varies considerably, but averages
about 5576, both in the lamb and previable human fetus
(13, 14). The proportion of umbilical venous blood pass-
ing through the ductus venosus is increased to 60 to 65%
during fetal hypoxemia, induced by administering a low-
oxygen gas mixture to the mother (15). During this type
of hypoxemia, the total umbilical venous return is not
changed, so that actual ductus venosus flow is increased.
In the condition of stress related to reduction of fetal
blood volume (16) or to compression of the umbilical
cord (17), umbilical venous return is reduced, but the
proportion passing through the ductus venosus is in-
creased. It thus appears that, during fetal stress, there is
preferential flow of oxygenated blood returning to the
fetal body through the ductus venosus and that this
blood aids in the supply of oxygenated blood directly to
the fetus, bypassing the hepatic circulation. Whether this
is due to relaxation of the ductus venosus sphincter, or
to decreased vascular conductance in the liver, is yet to
be delineated.
DISTRIBUTION OF DUCTUS VENOSUS AND
INFERIOR VENA CAVAL BLOOD
Previously, it had been shown that almost all the blood
returning to the heart from the superior vena cava is
directed across the tricuspid valve to the right ventricle,
while a minimal amount crosses the foramen ovale (11).
This streaming pattern was thought to account for the
higher oxygen saturation in left ventricular and ascending
aortic blood (55 to 60%) as compared with right ventric-
ular and pulmonary arterial blood (40to 45%).Descend-
ing aortic blood, largely derived from pulmonary arterial
blood traversing the ductus arteriosus, with a small con-
tribution from the ascending aorta, has a saturation of 50
to 55%.Recent studies have shown, however, that venous
streamlining in the inferior vena cava contributes to
these differences in oxygen saturation in the upper and
lower portions of the body in the fetus.
Ductus venosus blood enters the inferior vena cava at
the level of the hepatic veins. It had generally been
assumed that the two streams of venous blood from the
distal inferior vena cava and the ductus venosus mixed
and were then distributed to the right atrium, as well as
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256 RUDOLPH HEPATOLOGY

Liver

400 I-i I

Left Right Coudole

+ Umbilical Vein
u Total DV Llver

Portal Vein
FIG.2. Blood flow to the left and right lobes of the liver, in relation to organ weight, is shown in the left panel. The left lobe is seen to receive
almost all its flow from the umbilical vein (UV), whereas the right lobe receives portal venous (PV) as well as umbilical venous blood. The rcght
panel shows the distribution of umbilical and portal venous blood. Note that somewhat more than half of umbilical venous blood passes through
the ductus venosus (DV), while almost all the portal venous blood passes to the liver [from Edelstone et al. (4)]. HA, hepatic artery.

to the left atrium through the foramen ovale. In the concentration in the ascending aorta. Glucose is trans-
fetus, the crista dividens, the upper edge of the foramen ferred from the mother to the fetus across the placenta,
ovale, straddles the entrance of the inferior vena cava and the streamlining pattern favors direction of glucose
into the atria so that blood enters both atria. In acute through the foramen ovale and thus to the upper body.
studies in the primate fetus, preferential streaming of Blood supply to the myocardium is supplied by branches
umbilical venous, as compared with distal inferior vena of the ascending aorta, and these organs receive relatively
caval blood, through the foramen ovale was shown (18). greater proportions of oxygen and glucose than do lower
We have confirmed this preferential streaming pattern body organs. The placenta receives its blood supply from
in chronically instrumented lamb fetuses in utero (19, the descending aorta, which has a greater proportion of
20). poorly oxygenated distal inferior vena caval blood.
Umbilical venous blood has an oxygen saturation of During hypoxemia produced by reducing inspired ox-
about 80 to 85%with a POz of about 30 to 35 torr, whereas ygen concentration in the mother, local vascular re-
distal inferior vena caval blood has an oxygen saturation sponses influence the distribution of blood flow. Thus,
of about 25 to 30% with a PO2 of about 13 to 15 torr. vasodilatation in the cerebral and coronary circulations
Observation of the thoracic portion of the inferior vena results in increased blood flow to these organs, and this
cava in the living fetus reveals that there are two streams aids in maintaining oxygen and substrate supply. How-
of blood: a well-oxygenated stream in the posterior left ever, the streamlining of umbilical venous and distal
portion and a poorly oxygenated stream in the anterior inferior vena caval blood is enhanced, and this causes an
right portion. When microspheres are injected simulta- actual increase in oxygen delivery to the heart and brain,
neously into the umbilical vein and the distal inferior despite the reduction in umbilical venous oxygen satu-
vena cava, the distribution of distal inferior vena caval ration (15).
blood differs from that of umbilical venous blood which
enters the inferior vena cava through the ductus venosus.
FETAL LIVER BLOOD FLOW
Ductus venosus blood streams preferentially through the
foramen ovale, to the left atrium and left ventricle, and Based on cineradiographic studies in exteriorized fetal
then into the aorta, to be distributed to the heart, brain, lambs, Barclay et al. suggested that the umbilical vein
head and upper extremities, and thorax. Lesser propor- supplied the left and central portions of the liver, while
tions of umbilical venous blood are distributed to the the portal vein supplied the right lobe (21). A similar
lower body. Distal inferior vena caval blood streams pattern of blood flow was suggested for the human fetus
preferentially through the tricuspid valve into the right by Lind (2). This concept, if correct, would imply that
ventricle which ejects it into the pulmonary trunk, and the right lobe of the liver receives considerably less
most of the blood is then directed through the ductus oxygen because portal venous oxygen saturation is only
arteriosus to the descending aorta and lower body organs. about 30% as compared with that of umbilical venous
These preferential pathways for umbilical venous and blood (80 to 85%).In support of this contention is the
distal inferior vena caval blood contribute not only to observation that the right liver lobe in the fetus has
higher oxygen saturation in ascending aortic as compared greater hematopoietic activity than does the left lobe
with descending aortic blood, but also to a higher glucose (22).

Vol. 3, No. 2, 1983 HEPATIC AND UUCTUS VENOSUS BLOOD FLOWS DURING FETAL LIFE
FIG.3. Valves partly covering the orifices of the joint orifices of the
left hepatic vein and ductus venosus (left) and the right hepatic vein,
with the inferior vena cava, are shown [from Bristow et al. (5)].
In order to measure the actual quantities and distri-
bution of umbilical venous, portal venous, and hepatic
arterial blood supplying the fetal liver, we used the
microsphere method (4). Microspheres with different
isotopic labels were injected simultaneously into an um-
bilical vein, a tributary of the portal vein, and the distal
inferior vena cava in chronically catheterized fetal lambs.
We found that blood flow to the fetal liver was very high,
and that umbilical venous blood was distributed to both
the right and left lobes of the liver. Seventy-five to 80%
of hepatic flow was derived from the umbilical vein.
However, portal venous blood supplied only the right
lobe; a small quantity ( 4 0 % ) passed through the ductus
venosus, but none entered the left lobe. Hepatic arterial
blood flow was quite low, representing only about 2% of
total liver blood flow. The proportions of umbilical ve-
nous, portal venous, and hepatic arterial blood distrib-
uted to each lobe of the liver, and the actual blood
flow to each lobe in relation to its weight, are shown in
Figure 2.
Fetal hypoxemia produced by reducing inspired oxygen
percentage in the mother caused liver blood flow to fall
by about 20%, and there was a somewhat greater reduc-
tion in flow to the right as compared with the left lobe.
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257
FIG. 4. Diagram showing venous flow patterns in the fetal lamb.
Umbilical venous blood is distributed to the left lobe of the liver,
through the ductus venosus and to the right lobe of the liver. Portal
venous blood passes almost exclusively to the right lobe, but a small
proportion enters the ductus venosus. Ductus venosus and left hepatic
venous blood preferentially pass through the foramen ovale, whereas
right hepatic venous and distal inferior vena caval blood are preferen-
tially directed through the tricuspid valve. Superior vena caval blood
almost all passes through the tricuspid valve. SVC, superior vena cava;
IVC, inferior vena cava; LHV, left hepatic vein; RHV, right hepatic
vein.
When umbilical blood flow was reduced by inflating a
balloon in the fetal descending aorta, liver blood flow was
markedly reduced, proportionately much more than duc-
tus venosus flow (17). Of particular interest was the
finding that the decrease in blood flow to the right lobe
was considerably greater than that to the left lobe; when
umbilical blood flow was markedly reduced to about 25%
of its normal level, blood flow to the right lobe was almost
completely curtailed. These differences in blood flow to
the left and right lobes of the fetal liver have raised the
possibility that during asphyxia1 stress, the right lobe is
more susceptible to lack of oxygen supply than the left;
this could explain the greater tendency for necrosis of the
right lobe of the liver in human infants who have suffered
perinatal asphyxia (23).
The differences in blood supply to the lobes of the fetal
liver have also raised questions regarding oxygen uptake
and metabolism in each lobe. In order to study oxygen
consumption and glucose uptake or release from each
lobe, we developed a technique for placing catheters into
the left and right hepatic veins, and maintaining them
chronically in conjunction with catheters in the umbilical
and portal veins, and the descending aorta, in fetal lambs
in utero (5). Blood flows were measured with radioactive
microspheres and oxygen, and glucose flux was calculated
from measurements of oxygen and glucose concentra-
tions in blood in each vessel entering and leaving the
liver. We found that oxygen consumption of the two
lobes was similar (approximately 4 ml per 100 gm liver
weight per min). Oxygen consumption of the two lobes

258 RUDOLPH
accounted for about 20% of total fetal oxygen consump-
tion. The liver showed no net uptake or release of glucose,
but during hypoxia, glucose was released by the liver.
DISTRIBUTION OF HEPATIC VENOUS BLOOD
The differences in blood supply to the left and right
lobes of the liver, with similar oxygen consumption, result
in blood in the left and right hepatic veins having differ-
ent oxygen saturations. Right hepatic venous blood has
a saturation of about 55%, similar to that present in the
descending aorta, whereas left hepatic venous oxygen
saturation is about 10 to 15% higher. In view of this
difference and the presence of streaming patterns in the
thoracic portion of the inferior vena cava, we examined
the distribution of hepatic venous blood by injecting
microspheres into these vessels, simultaneous with injec-
tions into the umbilical vein and distal inferior vena cava.
These studies demonstrated that left hepatic venous
blood, with a saturation higher than right hepatic venous
blood, tended to follow the distribution of umbilical
venous blood. It was preferentially directed through the
foramen ovale to the left atrium and ventricle and as-
cending aorta. Right hepatic venous blood, with its lower
oxygen saturation, followed the distribution pattern of
distal inferior vena caval blood, preferentially passing
through the tricuspid valve to the right ventricle, pul-
monary artery, and through the ductus arteriosus to the
descending aorta (Bristow and Rudolph, unpublished
observations).
The mechanisms responsible for this streaming of right
and left hepatic venous blood have not been delineated,
but in the sheep fetus the morphological features of the
hepatic vein and ductus venosus connections with the
inferior vena cava may favor streaming. The ductus
venosus joins the left hepatic vein just before they con-
nect with the inferior vena cava. There is a common
orifice for these two vessels, which is partly covered in
the inferior portion with a thin, transparent membranous
valve. The right hepatic vein connects with the inferior
vena cava somewhat more anteriorly, and it too is partly
covered on the inferior portion of the orifice by a similar
valve-like structure (5) (Figure 3). These membranous
structures are probably not true valves because they do
not completely cover the orifices, but they probably serve
to direct the blood streams entering the inferior vena
cava just below the diaphragm. It is not known how these
streaming patterns are altered with changes in the mag-
nitude of umbilical venous, hepatic venous, and inferior
vena caval flow. The human fetus does not demonstrate
the venous valves noted in the sheep, but there are
prominent ridges at the inferior orifices of the hepatic
veins which probably function in a similar manner to
direct flow. The patterns of flow of blood entering and
leaving the liver in the fetus are reviewed in Figure 4.
These flow patterns could potentially have important
effects on relative distribution of substrates and hor-
mones, as well as of oxygen, in the fetus. Thus, all
hormones released in the pancreas or gastrointestinal
tract, which enter the portal vein, will reach the right
lobe of the liver in high concentration, while the concen-
tration reaching the left lobe will be markedly lower,
after dilution by almost total fetal cardiac output. Also,
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HEPATOLOGY
after passing through the right lobe of the liver, these
hormones will preferentially be distributed to the lower
fetal body, and reach the heart and brain in relatively
low concentration. Similarly, adrenal gland hormones
entering the distal inferior vena cava would tend to be
present in higher concentration in the lower than the
upper portion of the body of the fetus. The impact of
these streaming patterns on hormonal distribution and
on metabolism and growth of different fetal organs re-
mains to be studied.
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