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

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Chapter | 7 The Erythrocyte: Physiology, Metabolism, and Biochemical Disorders
Hematocrit (%) Reticulocytes (%) 2,3DPG (mmol/l)
9
8
7
6
5
4
3
2
1
0
10
8
6
4
2
0
55
50
45
40
35
30
25
20
15
0 4 8 12 16 20 24 28 32 36 40 44 48 52
Weeks after birth
FIGURE 7-8 Changes in hematocrit, uncorrected reticulocyte
count, and RBC 2,3DPG content in dogs following birth. Values are
mean standard deviation (Harvey, unpublished, 1994) .
in the 10-fold increase in RBC 2,3DPG during the first 5
days of life in lambs ( Noble et al. , 1983 ). (1) Plasma glucose
increases from 40 to 100 mg/dl during the first 2 days
of life and allows for an increased consumption of glucose
by the glucose-permeable neonatal RBC. (2) The blood pH
increases during the first day of life and activates the PFK
enzyme, as evidenced by changes in RBC intermediates.
(3) Plasma P i concentration increases to a level sufficient to
increase GAPD activity at 3 days of age. (4) DPGM activity
in neonatal RBCs is 12-fold higher than that of adults. (5)
RBC PFK activity is still above adult values, but PK activity
has decreased to adult values by birth.
The decline in 2,3DPG in postnatal ruminant RBCs is
more gradual, requiring 1 to 2 months to reach adult values.
The whole blood P 50 is maintained, however, because
of concomitant decreases in fetal Hb and increases in adult
Hb types ( Aufderheide et al. , 1980 ; Blunt et al. , 1971 ;
Lee et al. , 1971 ; Zinkl and Kaneko, 1973b ). In goat RBCs,
HbC replaces most of the fetal Hb initially, but after 2
months, other adult Hbs begin to replace HbC ( Huisman et
al. , 1969 ). Goat RBCs containing predominantly HbC have
lower Hb oxygen affinity with a moderately increased Bohr
effect compared to RBCs containing other adult Hbs (e.g.,
HbA, HbB, HbD) ( Huisman et al. , 1969 ). Only a small
percentage of HbC is present in lambs up to 2 months of
age. The percentage of fetal Hb at birth varies from 70% to
100%. The signal to switch production of fetal Hb to HbA
in lambs appears to result from an inherent programming of
hematopoietic stem cells ( Wood et al. , 1985 ).
Rapid, but modest, increases in 2,3DPG and P 50 occur
after birth in horse RBCs ( Bunn and Kitchen, 1973 ). As
in ruminants, blood pH increases significantly within
1 h after birth ( Rose et al. , 1982 ). Plasma P i concentration
also increases during the first 2 weeks of life ( Bauer et al. ,
1984 ). Gradual, but large, increases in 2,3DPG and P 50 occur
postnatally in blood of dogs ( Dhindsa et al. , 1972 ; Harvey
and Reddy, 1989 ; Mueggler et al. , 1980 ) and pigs ( Baumann
et al. , 1973 ; Kim and Duhm, 1974 ; Watts and Kim, 1984 ).
A decreasing activity of PK has been reported to account for
the increasing 2,3DPG concentration during the first 60 days
of life in dogs ( Mueggler and Black, 1982 ), but activation of
PFK may also play a role in this increase.
In human RBCs, 2,3DPG increases slightly after birth,
but most of the increase in P 50 that occurs during the first 6
months of life results from the replacing of HbF with adult
Hbs ( Oski and Gottlieb, 1971 ). Whereas P 50 values changed
slightly in kittens after birth, RBC 2,3DPG values remained
in the normal adult range ( Dhindsa and Metcalfe, 1974 ).
Data concerning changes in these and other species have
been compiled by Isaacks and Harkness (1983) .
6 . RBCs as Sensors and Effectors of Local O 2
Delivery
RBCs may also have a role in the regulation of local O 2
delivery to tissues that is mediated by Hb O 2 saturation
(SO 2 ). In addition to releasing O 2 from Hb in the tissues,
one or more signals are released from RBCs that trigger
vasodilation and increased blood flow to the feeding arterioles
( Jagger et al. , 2001 ; Singel and Stamler, 2005 ). Nitric
oxide (·NO), generated from L-arginine by ·NO synthases
in the endothelium and in other cells, is a potent vasodilator.
Some evidence suggests that ·NO can be transported by
RBCs to microvascular sites of action in a protected form
as an S-nitrosothiol on the highly conserved Hb β -93 cysteine
residue. On the release of oxygen, this S-nitrosoHb
purportedly delivers ·NO to arterioles ( Singel and Stamler,
2005 ). An alternate mechanism of ·NO delivery has been
proposed that reutilizes nitrite formed when ·NO reacts
with OxyHb ( Crawford et al. , 2006 ). Nitrite is stored
within RBCs and reduced back to ·NO by DeoxyHb, which
serves as a nitrite reductase ( Rifkind et al. , 2006 ). Both