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

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Chapter | 7 The Erythrocyte: Physiology, Metabolism, and Biochemical Disorders
Marked acanthocytosis is reported to occur in young
goats ( Holman and Drew, 1964 ) and some young cattle
( McGillivray et al. , 1985 ; Sato and Mizuno, 1982 ).
Acanthocytosis of young goats reportedly occurs as a result
of the presence of HbC at this stage of development ( Jain
et al ., 1980 ). Normal adult angora goats ( Jain et al. , 1980 ;
Jain and Kono, 1977 ) and some breeds of British sheep
( Evans, 1968 ) have variable numbers of fusiform or spindle-shaped
RBCs that resemble sickle cells (drepanocytes)
in normal deer and people with sickle cell anemia ( Taylor,
1983 ). Drepanocyte formation in deer depends on the
Hb types present. It is an in vitro phenomenon that occurs
when oxygen tension is high and pH is between 7.6 and 7.8
( Taylor, 1983 ). The proportion of fusiform cells in angora
goats varies depending on the individual and in vitro alterations
in temperature, pH, and oxygenation, but the tendency
to form fusiform cells could not be attributed to differences
in Hb type ( Jain and Kono, 1977 ). Echinocytosis is a consistent
artifact in stained blood films from pigs ( Harvey, 2001 ).
B . Functions of RBCs
The RBC functions of oxygen transport, carbon dioxide
transport, and hydrogen ion buffering are interrelated. Each
Hb tetramer can bind four molecules of oxygen when fully
saturated, forming oxyhemoglobin (OxyHb). Assuming a
normal arterial pO 2 of 100 mmHg and an Hb concentration
of 150 g/l (15 g/dl) in blood, the presence of Hb-containing
RBCs increases the oxygen carrying capacity of blood
approximately 70 times that which could be transported
dissolved in plasma ( West, 1985 ).
Approximately 10% of CO 2 is transported dissolved in
blood, 5% to 10% is transported bound to amine groups of
blood proteins, and 80% to 85% is transported in the form
of bicarbonate in normal individuals ( Hsia, 1998 ; Jensen,
2004 ). Carbonic acid is formed when dissolved CO 2 combines
with water. This reaction occurs nonenzymatically
but is accelerated by the presence of the carbonic anhydrase
(CA), also called carbonate dehydratase, enzyme in RBCs.
Bicarbonate is formed by the rapid spontaneous dissociation
of carbonic acid as shown:
CA
HOCO ←⎯⎯⎯→HCO ←⎯⎯→
H HCO
2 2
2 3 3
Hb potentiates the formation of bicarbonate by buffering
hydrogen ions and shifting the equilibrium of the reaction
to the right. Carbamino groups are formed by the combination
of CO 2 with the terminal groups of proteins. The globin
of Hb is the most important blood protein in this regard.
The transportation of CO 2 from the tissues to the lungs as
carbamino groups is potentiated because deoxyhemoglobin
(DeoxyHb) binds twice as much CO 2 as OxyHb. The formation
of carbamino groups can be represented as follows:
Hb-NH CO ↔Hb-NHCOOH↔Hb-NHCOO H
2 2
Hb is the most important protein buffer in blood because
it occurs in high concentration, has a relatively low molecular
weight, and has a large number of histidine residues with
p K a values close to 7.4, enabling them to function as effective
buffers. It has about six times the buffering capacity of
the plasma proteins. An additional factor of importance in
contributing to the effectiveness of Hb as a blood buffer is
the fact that DeoxyHb is a weaker acid than OxyHb. As a
result, most of the H produced in the tissues under normal
conditions is buffered as a direct result of the H uptake by
DeoxyHb owing to an increase in effective p K a of Hb following
release of oxygen to the tissues ( West, 1985 ).
II . HEMATOPOIESIS
A . Stem Cells and Progenitor Cells
Primitive hematopoietic stem cells (HSCs) appear to develop
in the embryo from a common precursor cell for both endothelial
and hematopoietic lineages. The first HSCs appear to
develop as clusters of cells in the wall of the dorsal aorta,
with subsequent development in the yolk sac, placenta, and
fetal liver ( Baron and Fraser, 2005 ). Beginning in midgestation
and continuing throughout postnatal life, mammalian
blood cells are produced continuously from HSCs within
extravascular spaces of the bone marrow. HSCs are capable
of proliferation, life-long self-renewal, and differentiation.
HSCs replicate only once every 8 to 10 weeks ( Abkowitz
et al. , 2002 ). The term hematopoietic progenitor cell (HPC)
refers to cells that form colonies in bone marrow culture like
HSCs but do not have long-term self-renewal capacities.
HSCs and HPCs are mononuclear cells that cannot be distinguished
morphologically from lymphocytes. The presence
of a transmembrane glycoprotein termed cluster of differentiation
antigen 34 (CD34) has been used to identify HSCs
and early HPCs, but some HSCs (possibly inactive ones)
lack CD34 ( Gangenahalli et al. , 2006 ). In addition, CD34 is
also present on the surface of nonhematopoietic stem cells
and vascular endothelial cells ( Kucia et al. , 2005 ; Wu et al. ,
2005 ). CD34 is believed to play a role in cell adhesion
(Gangenahalli et al. , 2006 ).
The most primitive HSC has the capacity to differentiate
into HPCs of all blood cell lineages and several cell
types in tissue. The frequency of HSCs in the marrow is
estimated to be 0.01% of nucleated marrow cells in adult
mice and 0.0001% of nucleated marrow cells in adult
cats ( Abkowitz et al. , 2002 ). HSCs produce HPCs that can
give rise to one or more blood cell types. HPCs are much
more numerous in marrow than are HSCs. Less than 2% of
nucleated bone marrow cells in adult dogs are CD34 , but
up to 18% CD34 cells have been reported in neonatal pups
(Faldyna et al. , 2003 ; Suter et al. , 2004 ). A common lymphoid
progenitor cell is believed to give rise to B lymphocytes,
T lymphocytes, lymphoid dendritic cells, and natural
killer cells ( Blom and Spits, 2006 ). A common myeloid