Clinical Biochemistry of Domestic Animals (Sixth Edition) - UMK ...

IV. Mature RBC
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RBC 2,3DPG increases in some anemic animals ( Agar
et al. , 1977 ; King et al. , 1992 ; Paltrinieri et al. , 2000 ;
Studzinski et al. , 1978 ). The resultant increase in P 50 would
seem to be beneficial in response to anemia. Increased
2,3DPG has also been reported in RBCs from horses with
hypoxic conditions ( Giordano et al. , 2004 ). When humans
and animals enter higher altitude, their ventilation frequency
increases. This hyperventilation decreases the pCO 2
and increases arterial pH, which increases the oxygen affinity
for Hb. However, the increased pH stimulates RBC glycolysis
and 2,3DPG synthesis, which tends to counteract the
effect of increased pH. This response is appropriate as long
as the increased ventilation can maintain alveolar O 2 tension
sufficient for O 2 loading in the lungs ( Nikinmaa, 2001 ). In
the case of severe hypoxic hypoxemia the response might
be detrimental, because Hb cannot be fully saturated
( Jensen, 2004 ). Various studies in dogs indicate that cardiac
output and microcirculation adjustments are much more
important than changes in Hb oxygen affinity in adapting to
hypoxia ( Liard and Kunert, 1993 ; Schumacker et al. , 1985 ;
Zachara et al. , 1981 ). However, a reduction in Hb oxygen
affinity secondary to increased 2,3DPG can be beneficial,
because it is far less energy demanding than is an increase
in cardiac output ( Liard and Kunert, 1993 ; Mairbäurl, 1994 ;
Teisseire et al. , 1985 ). RBC 2,3DPG increases in hibernating
mammals, but the effect of the decrease in body temperature
associated with hibernation on Hb oxygen affinity in
vivo would more than offset the effect of increased 2,3DPG
( Bunn, 1981 ). Because pH has a substantial effect on Hb
oxygen affinity, changes in RBC 2,3DPG concentration, in
response to acidosis and alkalosis, produce effects on Hb
oxygen affinity that counteract alterations induced by the
respective changes in pH ( Bellingham et al. , 1971 ).
Aged human RBCs lose K , organic phosphates (especially
2,3DPG), and water. The loss of organic phosphates
results in increased Hb oxygen affinity in these older RBCs
(Schmidt et al. , 1987 ).
4 . Maternal-Fetal Oxygen Transport
Except for in the domestic cat, the oxygen affinity of Hb in
fetal blood is higher than that of maternal blood when measured
under standard conditions ( Bunn and Kitchen, 1973 ;
Novy and Parer, 1969 ). This difference in oxygen affinity
probably enhances the transport of oxygen across the placenta
to the fetus ( Comline and Silver, 1974 ; Hebbel et al. ,
1980 ). Oxygen is adequately transported to cat fetuses,
without the advantage of increased oxygen affinity, because
of the nature of the placentation and a countercurrent
arrangement of blood flows ( Novy and Parer, 1969 ).
During late gestation, mean umbilical venous pO 2 values
of 48, 38, 35, and 30 mmHg have been reported for
horses, cattle, sheep, and pigs, respectively ( Comline and
Silver, 1974 ). Fetal systemic arterial pO 2 values may be
even lower, especially in species such as the pig and horse,
which lack a ductus venosus, requiring that all returning
umbilical venous blood pass through the liver. These pO 2
values are considerably lower than normal adult arterial
pO 2 values of about 100 mmHg. Because Hb in adult RBCs
of these species is only partially saturated at these low arterial
pO 2 values ( Schmidt-Neilsen and Larimer, 1958 ), the
increased oxygen affinity of fetal blood would result in a
greater saturation of Hb and, therefore, a greater oxygencarrying
capacity of blood than would otherwise be present.
Fetal RBCs maintain Hb oxygen affinities higher than
those of the mother by one of three mechanisms ( Bunn and
Kitchen, 1973 ). (1) Ruminants have structurally distinct
fetal Hbs that have higher oxygen affinities than adult Hbs
in the absence of organic phosphates ( Battaglia et al. , 1970 ;
Blunt et al. , 1971 ). Interactions between 2,3DPG and both
fetal and adult Hbs in ruminants are weak when Cl is present
( Bunn and Kitchen, 1973 ). (2) A structurally distinct
fetal Hb (HbF) also occurs in humans, but the oxygen affinity
of stripped HbF and adult human Hb is about the same.
Differences in whole blood oxygen affinity occur primarily
because HbF interacts weakly with 2,3DPG, in contrast to
the strong interaction with adult Hbs ( Oski and Gottlieb,
1971 ). (3) Animals without structurally distinct fetal Hbs,
such as dog, horse, and pig, have much lower 2,3DPG
concentrations in fetal RBCs than in adult RBCs, thereby
creating higher oxygen affinities in fetal RBCs ( Bunn and
Kitchen, 1973 ; Comline and Silver, 1974 ; Dhindsa et al. ,
1972 ; Tweeddale, 1973 ). The actual in vivo difference in
oxygen affinity between fetal and maternal RBCs is presumably
less than suggested by differences in P 50 values measured
in vitro at pH 7.4, because fetal blood pH is lower than
that of maternal blood ( Comline and Silver, 1974 ). However,
the diffusion of CO 2 from fetal blood to maternal blood
helps increase the pH and oxygen affinity in fetal blood,
and it simultaneously decreases the pH and oxygen affinity
in maternal blood. This “ double Bohr effect ” enhances the
mother-to-fetus O 2 transfer ( Zhang et al. , 2003 ).
5 . Postnatal Changes in 2,3DPG and Oxygen
Affi nity
Although the higher oxygen affinity of Hb in fetal RBCs
may be beneficial in the uterus, it would seem to be disadvantageous
to the newborn animal breathing air. Whole
blood P 50 values and RBC 2,3DPG concentrations ( Fig. 7-8 )
increase after birth in most domestic animals.
RBC 2,3DPG concentrations are higher in fetuses than
in adult ruminants, and they increase markedly within a few
days after birth ( Aufderheide et al. , 1980 ; King and Mifsud,
1981 ; Zinkl and Kaneko, 1973a ). Because neither fetal
nor adult Hbs from ruminants bind 2,3DPG to any extent
(at least in the presence of physiological concentrations of
Cl ), 2,3DPG decreases oxygen affinity primarily by lowering
intracellular pH ( Aufderheide et al. , 1980 ; Battaglia
et al. , 1970 ; Blunt, 1972 ). Several mechanisms are involved