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

References
279
( Norrdin et al ., 2004 ). The cause of this disorder in cattle
is unknown, but the findings that BMPs can stimulate hepcidin
expression ( Truksa et al ., 2006 ), and that deficient
BMP activity can result in osteopenia ( Rosen, 2006 ), suggest
that a BMP defect or a BMP signal transduction pathway
defect should be investigated.
7 . Idiopathic Hemochromatosis
Idiopathic hemochromatosis with hepatic cirrhosis and
biliary hyperplasia has been described in three full-sized
horses (14 years to 16 years old) and an 11-year-old racing
pony ( Lavoie and Teuscher, 1993 ; Pearson et al ., 1994 ).
Hepatocytes and Kupffer cells contained markedly increased
stainable iron in all horses, and iron accumulations were
noted outside the liver in tissues including the epithelium of
large bile ducts, follicular epithelium of the thyroid gland,
cortical tubules of the kidneys, and in the neurohypophysis in
the pony ( Lavoie and Teuscher, 1993 ). Iron can accumulate
in the liver of animals with chronic liver disease; consequently,
one might speculate that the full-sized horses had
primary liver disease with secondary iron accumulation
(Pearson et al ., 1994 ; Schultheiss et al ., 2002 ). However,
iron accumulation secondary to chronic liver disease is
reported to occur in Kupffer cells and macrophages, but not
hepatocytes ( Schultheiss et al ., 2002 ). The widespread iron
deposition in the pony is similar to that seen in people with
hereditary hemochromatosis.
F. Siderotic Inclusions in Erythroid Cells
Anucleated erythrocytes containing siderotic inclusions are
called siderocytes. Nucleated siderocytes have been called
sideroblasts in human hematology, in which terminology
used for erythrocyte precursors is generally different from
that conventionally used in veterinary hematology ( Bottomley,
2004 ). Siderotic inclusions in erythroid cells may consist
of cytoplasmic ferritin aggregates or iron-loaded mitochondria.
Ferritin aggregates can occur normally in nucleated
erythroid cells, but the presence of iron-loaded mitochondria
is a pathological finding ( Cartwright and Deiss, 1975 ).
Electron microscopy is used to definitively identify the nature
of siderotic inclusions ( Fresco, 1981 ; Hammond et al ., 1969 );
however, the location of iron-positive inclusions in a ring
around the nucleus of a nucleated siderocyte (termed ringed
sideroblast in human hematology) strongly suggests the presence
of iron-loaded mitochondria ( Bottomley, 2004 ).
Except for iron deficiency, disorders in heme synthesis
have the potential to cause excess iron accumulation in
mitochondria ( Beutler, 1995 ; Fairbanks and Beutler, 1995 ).
Chronic copper deficiency, as a cause for the formation of
siderotic inclusions, was discussed previously. Pyridoxine,
vitamin B 6 , is required for the first step in heme synthesis,
and erythroid cells with iron-loaded mitochondria have
been documented in pigs fed a pyridoxine-deficient diet
( Hammond et al ., 1969 ). Drugs or chemicals reported to
cause siderocytes or nucleated siderocytes in dogs include
chloramphenicol ( Harvey et al ., 1985 ), lead, hydroxyzine,
zinc ( Harvey, 2001 ), and an oxazolidinone antibiotic ( Lund
and Brown, 1997 ).
Siderotic inclusions in erythroid cells have been recognized
in some dogs and cats with myeloproliferative disorders
( Blue et al ., 1988 ; Weiss and Lulich, 1999 ). Acquired
dyserythropoiesis with siderocytes have been reported
in dogs in which specific etiologies could not be determined,
although some of these animals had inflammatory
disorders ( Canfield et al ., 1987 ; Weiss, 2005 ). Persistent
siderotic inclusions have been recognized in microcytic
hypochromic erythrocytes from an English bulldog.
Erythrocytes also contained Heinz bodies and rare hemoglobin
crystals ( Harvey et al ., 2007 ). A congenital defect
resulting in mitochondrial iron overload and secondary
oxidant injury was suspected but not identified.
Congenital anemias with ringed nucleated siderocytes
have been reported in humans but not in domestic animals
(Bottomley, 2004 , 2006 ). Inherited causes recognized in
humans include defective eALAS, adenosine triphosphatebinding
cassette 7 (ABC7) transporter, glutaredoxin 5, thiamine
transporter, pseudouridine synthase I, and respiratory
chain components ( Bottomley, 2006 ; Camaschella et al .,
2007 ). Siderotic inclusions occur in erythroid cells of mice
genetically altered to produce eALAS deficiency ( Nakajima
et al ., 2006 ) and mitochondrial superoxide dismutase 2 deficiency
( Friedman et al ., 2004 ).
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