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

184
Chapter | 7 The Erythrocyte: Physiology, Metabolism, and Biochemical Disorders
rare in adult cats ( French et al. , 1987 ; Fulton et al. , 1988 )
and horses ( Smith et al. , 1986 ), but it occurs frequently in
ruminants that are heavily parasitized with blood-sucking
parasites such as Haemonchus contortus . Much more information
concerning iron deficiency is given in Chapter 9 .
Prolonged copper deficiency generally results in anemia
in mammals ( Auclair et al. , 2006 ; Brewer, 1987 ; Lahey et al. ,
1952 ), although anemia was not a feature of experimental
copper deficiency in the cat ( Doong et al. , 1983 ). The anemia
is generally microcytic hypochromic; however, normocytic
anemia has been reported in experimental studies in dogs,
and normocytic or macrocytic anemias have been reported
in cattle and adult sheep ( Brewer, 1987 ). Copper deficiency
results in impaired iron metabolism ( Lee et al. , 1968b ). In
experimental studies in pigs, serum iron concentration is
low in early copper deficiency when iron stores are normal
(Lahey et al. , 1952 ; Lee et al. , 1968b ). Functional iron deficiency
occurs because copper-containing proteins hephaestin
and ceruloplasmin are required for normal iron transport
(Lee et al. , 1968a ; Wessling-Resnick, 2006 ).
If experimental copper deficiency is prolonged in pigs,
hyperferremia occurs and nucleated erythroid cells with
cytoplasmic siderotic (iron-positive) inclusions increase in
bone marrow ( Lee et al. , 1968a ). Reticulocyte mitochondria
from copper-deficient pigs are unable to synthesize heme at
the normal rate using Fe 3 (Williams et al. , 1976 ). A deficiency
in copper-containing cytochrome oxidase within
mitochondria may slow the reduction of Fe 3 to Fe 2 within
mitochondria. That would limit heme synthesis, which
requires iron in the Fe 2 state ( Porra and Jones, 1963 ).
3 . Defi ciencies in Globin Synthesis
Hereditary deficiencies in synthesis of the globin α chain
( α -thalassemia) and β chain ( β -thalassemia) cause microcytic
hypochromic anemias in humans with variable
degrees of poikilocytosis ( Weatherall, 2006 ). Both α - and
β -thalassemia occur in mice, but thalassemias have not
been reported in domestic animals.
4 . Aplastic Anemia
Aplastic anemia is generally used to describe anemias
where granulocytic, megakaryocytic, and erythrocytic cell
lines are markedly reduced in the bone marrow. When only
the erythroid cell line is reduced or absent, terms such as
pure red cell aplasia , selective erythroid aplasia , or selective
erythroid hypoplasia are used.
Many drugs have been incriminated in the production of
aplastic anemia in humans ( Shadduck, 1995 ). Drug-induced
causes of aplastic anemia or generalized marrow hypoplasia
in animals include estrogen toxicity in dogs, phenylbutazone
toxicity in dogs and possibly a horse, trimethoprimsulfadiazine
administration in dogs, bracken fern poisoning
in cattle and sheep, trichloroethylene-extracted soybean
meal in cattle, albendazole toxicity in dogs and cats, griseofulvin
toxicity in cats, various cancer chemotherapeutic
agents, and radiation. Thiacetarsamide, meclofenamic
acid, and quinidine have also been incriminated as potential
causes of aplastic anemia in dogs. In addition to exogenous
estrogen toxicity, high levels of endogenous estrogens, produced
by estrogen secreting tumors and functional cystic
ovaries in dogs and prolonged estrus in ferrets, can result in
aplastic anemia ( Harvey, 2001 ). Parvovirus infections can
cause erythroid hypoplasia, as well as myeloid hypoplasia
in canine pups ( Potgieter et al. , 1981 ; Robinson et al. ,
1980 ), but animals may not become anemic, because of the
long life spans of RBCs. Although some degree of marrow
hypoplasia or dysplasia often occurs in cats with feline leukemia
virus (FeLV) infections ( Cotter, 1979 ), true aplastic
anemia is not a well-documented sequela ( Rojko and Olsen,
1984 ). Hypocellular bone marrow has been reported in cats
experimentally co-infected with FeLV and feline parvovirus
(Lutz et al. , 1995 ). Dogs with acute Ehrlichia canis infections
may spontaneously recover or develop chronic disease
that generally exhibits some degree of marrow hypoplasia.
Although rare, aplastic anemia may develop in association
with severe chronic ehrlichiosis in dogs ( Neer, 1998 ).
A retrospective review of cats with aplastic anemia
identified 13 cases in which the clinical diagnoses included
chronic renal failure (n 5), FeLV infection (n 2),
hyperthyroidism treated with methimazole (n 1), and
idiopathic aplastic anemia (n 5). The author suggested
that starvation may have played a role in the development
of marrow aplasia in some of these cats ( Weiss, 2006 ).
Idiopathic aplastic anemia has also been reported in dogs
and horses ( Harvey, 2001 ). CFU-E were not detected in
bone marrow culture from a dog with an idiopathic aplastic
anemia ( Weiss and Christopher, 1985 ).
Other potential causes of aplastic anemia include congenital
defects and primary immune-mediated disorders.
Most cases of aplastic anemia in adult humans are immune
mediated, with activated type 1 cytotoxic T cells implicated
in the pathogenesis ( Young et al. , 2006 ). The aberrant
immune response may be triggered by environmental exposures,
such as to chemicals and drugs or viral infections,
and possibly by endogenous antigens generated by genetically
altered bone marrow cells ( Young, 2002 ).
5 . Selective Erythroid Aplasia
Selective erythroid aplasia (pure red cell aplasia) occurs as
either a congenital or acquired disorder in people. Acquired
erythroid aplasia is often associated with abnormalities
of the immune system. Erythroid aplasia may also occur
secondary to disorders such as B-19 parvovirus infection,
lymphoid malignancies, and drug or chemical toxicities
( Erslev and Soltan, 1996 ).
Acquired erythroid hypoplasia or aplasia occurs in
dogs ( Stokol et al. , 2000 ; Weiss, 1986 ). Some cases have