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

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Chapter | 7 The Erythrocyte: Physiology, Metabolism, and Biochemical Disorders
In situ
Band 4.2 has not been demonstrated in some species
including horses ( Guerra-Shinohara and Barretto, 1999 ).
The cytoskeletal meshwork assumes a condensed configuration
in nondeformed discocytes, with spectrin tetramer
fibers existing in folded or coiled states ( Fig. 7-4 ). When fully
extended (accomplished by removal of lipid from the membrane),
the cytoskeleton meshwork extends over an area
several times the normal RBC surface area ( Liu and Derick,
1992 ; Palek and Sahr, 1992 ). Because of the spectrin
structure, membrane skeletons have extensional elasticity
and can be stretched more than twice the normal RBC
diameter without rupture.
B . Shape and Deformability
Spread
FIGURE 7-4 Schematic model of a hexagon of condensed and fully
extended (spread) cytoskeletal meshwork. Spectrin dimer-dimer interactions
and binding to band 3 occur in the midregions. See Figure 7-3 for
components of junctional complexes.
The normal biconcave shape of most mammalian RBCs
(discocytes) represents the resting unstressed geometry
of the cell. The biconcave shape results in a large surface
area-to-volume ratio compared to that of a sphere, allowing
RBCs to undergo marked deformation while maintaining
a constant surface area ( Lenard, 1974 ). This is important
because an increase of 3% to 4% of surface area results in
cell lysis ( Mohandas and Chasis, 1993 ).
The RBC spends little time in a discoid shape in the
microcirculation. Except for goats, RBCs from domestic
animals have diameters ( Jain, 1986 ) greater than those of
capillaries (approximately 4 μm) (Henquell et al. , 1976 ;
Sobin and Tremer, 1972 ); consequently, they must be
deformable to flow through capillaries. RBCs must pass
through even smaller spaces in the sinus wall of the spleen
( Chen and Weiss, 1973 ). The biconcave shape is generally
more pronounced in species with larger RBCs ( Harvey,
2001 ), presumably because the degree of deformation
required to flow through capillaries is greater. RBC deformability
also reduces bulk viscosity of blood in large vessels
(Smith, 1991 ).
RBC deformability is a function of surface-to-volume
ratio, viscosity of intracellular contents (determined primarily
by intracellular Hb concentration), and viscoelastic
properties of the membrane ( Mohandas and Chasis, 1993 ).
RBC shape and viscoelastic properties result from interactions
between the fluid lipid bilayer and the underlying cytoskeleton,
which stabilizes the lipid bilayer and provides both
rigid support and elasticity. Membrane lipid fluidity varies
with the cholesterol composition, concentration of phospholipids
present, and the degree of saturation of fatty acids and
length of acyl chains ( Yawata et al. , 1984 ). Comparisons
of RBC deformability among various animal species using
ektacytometry have been reported ( Smith et al. , 1979 ). Large
RBCs are generally more deformable than small ones. RBCs
from species in the family Camelidae are flat, thin, and not
deformable; they apparently flow through vessels by orienting
to the direction of flow.
In addition to mechanically induced deformations, a
wide variety of chemical perturbations, genetic defects, and
oxidative injury can result in shape changes ( Mohandas and
Chasis, 1993 ; Smith, 1987 ). Small changes in the surface
areas of the inner or outer lipid monolayers can result in
transformations of discocytes into echinocytes or stomatocytes.
Biochemical abnormalities associated with certain
RBC shape abnormalities follow in this text. Consult a reference
text for additional information about these and other
RBC shape abnormalities ( Harvey, 2001 ).
1 . Echinocytes
Echinocytes are spiculated RBCs in which the spicules
are relatively evenly spaced and of similar size. When
observed in stained blood films, echinocytosis is usually
an artifact that results from excess EDTA, improper smear
preparation, or prolonged sample storage before blood film
preparation. Echinocytes form when the surface area of the
outer lipid monolayer increases relative to the inner monolayer.
Echinocytic transformation occurs in the presence of
fatty acids, lysophospholipids, and amphiphatic drugs that
distribute preferentially in the outer half of the lipid bilayer
( Mohandas and Chasis, 1993 ; Smith, 1987 ). Transient
echinocytosis occurs in horses with Clostridium perfringens
infection and in dogs following coral snake ( Marks
et al. , 1990 ) and rattlesnake ( Brown et al. , 1994a ; Hackett
et al. , 2002 ) envenomation, presumably secondary to the
action of phospholipases present in venom ( Walton et al. ,
1997 ). Echinocytes also form when RBCs are dehydrated
( Weiss and Geor, 1993 ), pH is increased, intracellular calcium
is increased ( Smith, 1987 ), and RBC ATP is depleted
( Backman et al. , 1998 ; Jacob et al. , 1973 ). Echinocytes are
the predominant RBC shape abnormality in human burn
patients ( Harris et al. , 1981 ).
Echinocytosis occurs in horses in which total body
depletion of cations has occurred. Increased numbers have
been reported in horses during endurance exercise ( Boucher
et al. , 1981 ), following furosemide-induced electrolyte
depletion ( Weiss et al. , 1992b ), and in ill horses with systemic
electrolyte depletion and hyponatremia ( Geor et al. ,
1993 ).