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

IV. Mature RBC
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Pig RBC isoantigens are recognized to occur in 16
blood groups numbered A to P ( Penedo, 2000 ). A-negative
pigs exhibit intravascular hemolysis when transfused with
A-positive blood. Neonatal isoerythrolysis has been recognized
in pigs, with antibodies usually directed against isoantigens
of the E blood group ( Tizard, 2000 ).
Naturally occurring neonatal isoerythrolysis has not
been reported in cattle, but it occurs in some calves born
to cows previously vaccinated for anaplasmosis or other
bovine origin vaccines containing RBC membranes
( Dimmock and Bell, 1970 ; Luther et al. , 1985 ). Several
blood group isoantigens have been incriminated, but the
most important blood group isoantigens involved in this
disorder are uncertain ( Dimmock and Bell, 1970 ). Based
on experimentally produced disease, the B isoantigen group
appears to generate potent hemolysins ( Dimmock et al. ,
1976 ).
2 . Natural Antibodies
Some blood group systems, such as the ABO group in
humans, the AB group and Mik group in cats, and the A
group in pigs, are characterized by “ naturally occurring ”
antibodies (i.e., antibodies occur in plasma in the absence
of prior exposure to blood from another individual) ( Tizard,
2000 ; Weinstein et al. , 2007 ). In other blood groups, such
as the Rh system in humans and most blood groups in animals,
antibody formation results from prior exposure to
different RBC isoantigens via transfusion, pregnancy, or
vaccination with products containing blood group antigens
( Stormont, 1982 ). Fortunately, naturally occurring antibodies
of clinical significance seldom occur in animals;
consequently, adverse transfusion reactions to unmatched
RBCs generally do not occur at the time of the first blood
transfusion. However, exceptions may occur as in the case
of the AB group in cats where B-positive cats have naturally
occurring anti-A antibodies with high hemolytic titer
( Bücheler and Giger, 1993 ).
D . Membrane Transport
The lipid bilayer is impermeable to most molecules.
Consequently, various membrane protein transport systems
are utilized for movement of molecules into and out
of RBCs.
1 . Anions and Water
Water and CO 2 are transported across RBC membranes
using water channels called aquaporins ( Endeward et al. ,
2006 ; Kuchel and Benga, 2005 ). Band 3 appears to function
as a channel for the movement of anions, especially
bicarbonate and chloride, certain nonelectrolytes, and
probably cations to some extent ( Bruce, 2006 ; Solomon
et al. , 1983 ). Gruber and Deuticke studied phosphate as a
model for anion exchange in RBCs from several species.
There was a positive correlation between phosphate influx
and the proportion of phosphatidylcholine in membrane
phospholipids ( Gruber and Deuticke, 1973 ).
2 . Sodium and Potassium
Major interspecies, and in some cases intraspecies, differences
occur in cation transport and subsequently in intracellular
Na and K concentrations ( Ellory and Tucker,
1983 ). There is a strong positive correlation between intracellular
K /Na
ratio and ATP concentration when RBCs
of different species are compared. The cause of this relationship
is unknown, but it is not related to differences in
glucose utilization ( Miseta et al. , 1993 ).
Like humans, those animal species with high intracellular
K concentrations, horse, pig, and some ruminants, have
an active Na ,K -pump that exchanges intracellular Na
for extracellular K with the hydrolysis of ATP. This
Na ,K -activated ATPase activity is often used as a measure
of Na ,K -pump activity. In addition to individuals
with high potassium (HK ) RBCs, some sheep, goats, buffalo,
and most cattle have relatively low potassium (LK ),
and consequently high sodium, RBCs. These LK RBCs
have low Na ,K -pump activity and high passive K permeability
(i.e., high K -Cl cotransport) ( Dunham and
Blostein, 1997 ; Tosteson and Hoffman, 1960 ). Studies in
sheep and goats have demonstrated that HK /LK polymorphism
is determined by a single autosomal genetic
locus with 2 alleles, the LK allele being dominant ( Tunon
et al. , 1987 ; Xu et al. , 1994 ). In sheep, this polymorphism
is associated with an M and L blood group antigen polymorphism.
The HK cells exhibit M antigens and the
homozygous LK cells exhibit L antigens, with heterozygous
LK sheep exhibiting M and L antigens. There are
two classes of L antigen (Lp and Ll) that assort together.
The Lp antigen inhibits the Na ,K -pump, mainly by promoting
nonspecific inhibition by intracellular K . This
antigen also modulates pump differentiation in immature
cells. In contrast, the Ll antigen stimulates K -Cl
cotransport ( Dunham and Blostein, 1997 ).
RBCs from cats, ferrets, and most dogs do not have
Na ,K -pump activity and have Na and K concentrations
near, but not at, those predicted for the Donnan equilibrium
with plasma ( Mairbaurl and Herth, 1996 ; Parker, 1977 ).
Some clinically normal Japanese Akita dogs ( Degen, 1987 ),
mongrel dogs from Japan ( Inaba and Maede, 1984 ), and
Korean Jindo dogs ( Yamato et al. , 1999 ) have HK RBCs.
RBCs from the HK mongrel dogs have substantial Na ,K -
ATPase activity and altered amino acid metabolism which
are discussed later. Dog, ferret, and bear RBCs have a unique
Na -Ca 2 countertransport system that can remove sodium
( Parker, 1992 ). The calcium that enters the cell is subsequently
pumped out by an ATP-dependent calcium pump.