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

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Chapter | 9 Iron Metabolism and Its Disorders
TABLE 9-3 Laboratory Findings in Chronic
Iron Deficiency Anemia versus the Anemia of
Inflammatory Disease
Parameter
Hematocrit
Mean cell
volume
Serum iron
Iron Deficiency
Anemia
Slight to marked
decrease
Slight to marked
decrease
Slight to marked
decrease
this pattern appears to be chronic hepatitis, in which serum
iron and TIBC may be increased rather than decreased
(Soubasis et al ., 2006 ). Serum ferritin, bone marrow stainable
iron, and liver nonheme iron are increased with
inflammation (Feldman et al ., 1981a, 1981c). Serum ferritin
may be increased both as a result of increased iron
stores and because it is an acute phase protein ( Ottenjann
et al ., 2006 ; Smith and Cipriano, 1987 ). Hematological
aspects of the anemia of inflammatory disease are compared
to iron deficiency in Table 9-3 .
C. Portosystemic Shunts
Anemia of
Inflammatory
Disease
Slight to moderate
decrease
Normal to slight
decrease
Slight to moderate
decrease
Serum TIBC Normal to increased Normal to decreased
Serum ferritin Decreased Normal to increased
Marrow
hemosiderin
Decreased or absent
Abbreviation: TIBC, total iron-binding capacity.
Normal to increased
Vascular connections between the portal and systemic circulation
that preferentially divert portal blood around the
liver are called portosystemic shunts (PSS). They may be
congenital or develop secondary to portal hypertension
associated with chronic primary hepatobiliary disease
( Center and Magne, 1990 ).
Microcytosis occurs in approximately two-thirds of the
dogs with PSS. The cause of the microcytosis is not completely
understood, but it is associated with abnormal iron
metabolism. The MCV is seldom more than 7fl below the
reference interval and the hematocrit is within or slightly
below the reference interval. The MCHC is slightly
decreased and the RDW is slightly increased in a majority
of cases. Codocytes are commonly observed in dogs.
The MCV is slightly decreased in about one-third of the
cats with PSS. Poikilocytosis (keratocytes and elliptocytes)
is common, but anemia is not usually present ( Center and
Magne, 1990 ; Levy et al ., 1995 ).
About half of the dogs with PSS exhibit hypoferremia
with normal or slightly decreased serum TIBC. Serum ferritin
and stainable iron (hemosiderin) in the liver and bone
marrow are normal or high ( Bunch et al ., 1995 ; Doberneck
et al ., 1963 ; Laflamme et al ., 1994 ; Meyer and Harvey,
1994 ; Simpson et al ., 1997 ). Erythrocyte protoporphyrin
and serum ceruloplasmin concentrations are normal
( Bunch et al ., 1995 ). Although the animals are not truly
iron deficient, the low serum iron appears to be related to
the development of microcytosis ( Simpson et al ., 1997 ).
D. Copper Deficiency
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 ). Decreased hephaestin levels in intestinal enterocytes
of copper-deficient animals result in decreased iron release
from enterocytes into plasma because hephaestin facilitates
iron export by ferroportin ( Reeves et al ., 2005 ; Wessling-
Resnick, 2006 ). Copper deficiency in pigs results in a
marked decrease in circulating ceruloplasmin and decreased
release of iron from tissue stores. Administration of ceruloplasmin
to these copper-deficient pigs results in a prompt
release of iron into the circulation bound to transferrin ( Lee
et al ., 1968b ; Roeser et al ., 1970 ). Iron is diminished in the
liver of copper-deficient pigs but accumulates in the liver
of copper-deficient rats and mice, suggesting that intestinal
iron absorption may not be as compromised in copperdeficient
rodents ( Auclair et al ., 2006 ; Wessling-Resnick,
2006 ). Humans with hereditary aceruloplasminemia have
iron accumulation in liver and other tissues. Clinical signs
include diabetes, dementia, and retinal degeneration, but not
liver disease ( Hellman and Gitlin, 2002 ).
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