A. Jensen & R. Berger, JDP 1991, 16:181-207
The relation between O2 delivery and tissue oxygen consumption
Subsection taken from the review 'Fetal circulatory responses to oxygen lack'
A. Jensen & R. Berger
Department of Obstetrics and Gynaecology, University of Gießen, Klinikstraße 32, Gießen Germany
Journal of Developmental Physiology (1991) 16:181-207
It has been recognized for a long time that hypoxaemia and asphyxia cause both a redistribution of blood flow
(Campbell et al., 1967; Cohn et al., 1974; Ashwal et al., 1981; Jensen et al., 1987a,b, 1991, Itskovitz et al., 1987)
and a reduction in oxygen consumption (Fig. 6 a)(Acheson et al., 1957; Parer et al., 1968; Künzel & Moll, 1972;
Wilkening & Meschia 1983; Jensen et al., 1987b, 1991). However, only recently a direct relationship between
changes in oxygen delivery, i.e. oxygen content x blood flow, to peripheral organs and changes in fetal oxygen
consumption has been demonstrated during acute asphyxia (Jensen et al., 1987b)(Fig. 6 b,c). The authors
interpreted their findings as an important protective mechanism, which ensures the maintenance of oxydative
metabolism in central fetal organs during acute asphyxia, and there is accumulating evidence to support this view
(Braems et al. 1990, Braems & Jensen 1991, Jensen et al., 1991, Asakura et al., 1990).
It is, however, important to notice that this new concept is not at variance with the current understanding of the
relation between uterine - and/ or umbilical blood flow and fetal oxygen consumption. The relationship between
both utero-placental and umbilical blood flow and the oxygen consumption of the fetus is curvilinear (Parer et
al., 1968; Künzel & Moll, 1972; Künzel et al., 1977, Wilkening & Meschia, 1983, see Carter 1989 for review).
This implies that fetal oxygen consumption is fairly constant over a wide range of changes in blood flow through
the uterine and umbilical circulation. This phenomenon has been observed by many investigators and is largely
due to the reciprocal relationship between uterine - and/or umbilical blood flow and oxygen extraction (Clapp,
1978). Thus, depending on the reduction in oxygen delivered caused by the reduction in blood flow, the fetus can
increase the amount of oxygen extracted from the blood across both the utero-placental and the umbilical-
placental vascular bed, and across the arterio-venous vascular bed of each individual organ. Therefore, the
oxygen consumption of the whole conceptus, the fetus, and the individual organs will remain constant over a
A. Jensen & R. Berger, JDP 1991, 16:181-207
wide range of changes in oxygen delivery. Oxygen consumption will only decrease when oxygen extraction is
maximal and oxygen delivery is reduced further. However, during acute hypoxaemia and asphyxia this break
point at which tissue oxygen consumption starts to fall can be reached fairly rapidly, though in different organs
at different points in time. This is caused by carotid arterial chemoreceptor activation, which results in
differential peripheral vasoconstriction mediated largely through sympathetic pathways. Then, both oxygen
content and blood flow fall concomitantly, resulting in a dramatic fall in oxygen delivery to and oxygen
consumption by peripheral organs. Thus, during asphyxia, circulatory centralization is accompanied by
'metabolic centralization'. This important mechanism, which involves vascular chemoreflexes mediated in part
by the sympathetic nervous system has survival value for the fetus (Jensen et al., 1987b).
A number of observations in the fetus and in the adult have contributed to the fact that the possible conclusion
that during fetal asphyxia, oxygen delivery might determine oxygen consumption have been precluded for a long
time. These include, in the fetus, the constancy of oxygen consumption over a wide range of both uterine and
umbilical blood flow changes (see Carter, 1989, for review), in the adult the well-known fact that brain oxygen
consumption is constant over a wide range of oxygen partial pressures in the carotid artery, and the fact that
mitochondrial oxygen consumption is maintained until oxygen partial pressure falls below a 'critical PO2' of
approximately 1mmHg (see Siesjö, 1978, for review).
However, at close look, the traditional concept from adult physiology that cellular oxygen consumption is largely
unrelated to oxygen availability due to the existance of a very low 'critical PO2' has been challenged previously.
Rosenthal et al. (1976) have reported that cytochrome a3 is normally more than 20% reduced, and that any
decrease and increase in PO2 will cause reduction or oxidation of cytochrome a3, raising the question whether
there is a 'critical PO2' at all (Siesjö, 1978). Thus, the matter seems to requires some reconsideration, and there
are good reasons to believe that the relation between oxygen delivery and oxygen consumption may be different
in the fetus, indeed. This is supported by several observations. It has recently been demonstrated for whole cell
preparations (Wilson, Owen & Erecinska, 1979), various individual organs, e.g. the carotid body (Acker &
Lübbers,1977), the liver (Bristow, Rudolph, Itskovitz & Barnes, 1983), the kidney (Iwamoto & Rudolph, 1985),
organ parts (Jensen, Roman, Rudolph, 1991), and for the whole conceptus (Acheson, Dawes, Mott, 1957; Jensen
et al., 1987b) that in the fetus the amount of oxygen available determines the amount of oxygen consumed.
Therefore, on the basis of these pieces of conclusive evidence and on the premis that oxygen extraction is
maximal, it seems reasonable to conclude that the relation between the availability of oxygen and the
consumption of oxygen may be fundamentally different during fetal as compared with adult life, in that oxygen
delivery to the tissues determines oxygen consumption by these tissues (Dawes, 1962, Jensen et al., 1987b) (Fig.
Additional support for this important mechanism has been provided in vivo by studies on ventilated fetal sheep
in utero after snaring the umbilical cord (Asakura et al., 1990) and in vitro by studies on fetal skeletal muscle
cells (Braems & Jensen, 1991), myocardial cells (Braems, Dußler, Jensen, 1990) and glial cells in monolayer
culture (G. Braems, A. Peltzer, A. Jensen, unpublished observations). The in vitro studies confirmed the
observations in vivo showing that in fetal cells oxygen availability is a determinant of cellular oxygen
The evidence produced so far in vivo and in vitro suggests strongly that during fetal life on transition from
normoxia to hypoxia the fetus is able to reduce oxygen consumption by decreasing oxygen delivery to peripheral
organs (Jensen et al., 1987b, Braems & Jensen, 1991). This 'metabolic centralization' helps to maintain oxydative
metabolism in central organs by maintaining oxygen delivery to and oxygen consumption of the brain and heart,
when oxygen is at short supply (Cohn et al., 1974, Ashwal et al., 1981, Jensen et al., 1987b).
Conversely, on transition from hypoxia to normoxia the increase in oxygen delivery is paralleled by an increase
in cellular oxygen consumption and in metabolic drive in most fetal organs. This mechanism, which may be of
particular importance on transition from fetal to post-natal life, when oxygen delivery and oxygen consumption
rise (Dawes & Mott, 1959) warrants optimal cell function at any given state of oxygenation.
The fetal carcass largely consists of skin, muscle, bones and connective tissues. Blood flow to the carcass falls
during more severe maternal hypoxaemia or a reduction in uterine blood flow (Cohn et al., 1974; Jensen et al.,
A. Jensen & R. Berger, JDP 1991, 16:181-207
1991). It rises, however, during graded reduction in umbilical blood flow (Itskovitz et al., 1987). Interestingly,
oxygen consumption of the carcass decreases twice as much during uterine blood flow reduction (Jensen et al.,
1991) than during umbilical blood flow reduction (Itskovitz et al., 1987), even though in both studies total fetal
oxygen delivery is reduced by similar amounts, i.e. by 50%. This suggests that the delivery of oxygen to the
carcass, which is considerably lower in the former study, determines the consumption of oxygen in the carcass
(Fig. 11). This view is supported by findings in the studies in which uterine blood flow was arrested (Jensen et
al., 1987b) (Fig. 6). These studies provided first evidence that the amount of oxygen delivered to peripheral
organs determines the amount of oxygen consumed by these organs (Jensen et al., 1987b). This important
mechanism enables the fetus to conserve oxygen in peripheral organs, e.g. the carcass, to maintain oxydative
metabolism in central organs when oxygen is at short supply.
In summary, hypoxia and asphyxia cause centralization of the fetal circulation through chemoreceptor mediated
vascular reflexes, which involve, among other vasoactive mechanisms, the activation of the sympathetic nervous
system. This circulatory centralization acts in concert with a 'metabolic centralization', which maintains oxygen
delivery to, oxygen consumption of and cell function in the brain and heart to ensure intact survival of the fetus
(Jensen et al., 1987b, Jensen, 1991).
refer to https://www.researchgate.net/publication/21344116_Fetal_circulatory_response_to_oxygen_lack