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

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Chapter | 9 Iron Metabolism and Its Disorders
is needed for normal hemoglobin synthesis. A decrease
in MCV generally precedes a decrease in MCHC in irondeficient
animals ( Harvey, 2000 ). A low MCHC is often
present in severely affected dogs and ruminants, but it is
rarely present in iron-deficient horses or adult cats. The red
cell distribution width (RDW) is often increased because of
the presence of increased numbers of microcytes together
with normocytic cells.
Because reticulocytes are recently formed immature
erythrocytes, reticulocyte parameters may better reflect
the current state of iron sufficiency in an animal. A retrospective
study of dogs with natural disease found that low
MCV retic and low, CH retic were indicators of iron deficiency
( Steinberg and Olver, 2005 ). In addition to these parameters,
a prospective study of diet-induced iron deficiency in postweaning
dogs found that increased % Hypo retic , increased
% Low CH retic , decreased % High CH retic , and decreased %
Macro retic were indicators of iron deficiency ( Fry and Kirk,
2006 ). Of these various reticulocyte parameters, the CH retic
appears to be the most widely used in the diagnosis of iron
deficiency in humans ( Brugnara et al ., 2006 ).
Erythrocytes from dogs and ruminants with iron deficiency
anemia often appear hypochromic on stained blood
smears ( Harvey, 2001 ). In these species in which erythrocytes
appear as discocytes, hypochromic erythrocytes have
a narrow rim of lightly stained hemoglobin and greater
than normal area of central pallor. This hypochromasia
results from both decreased hemoglobin concentration
within cells and from the fact that the cells are thin (leptocytes).
Because these microcytic leptocytes have increased
diameter-to-volume ratios, they may not appear as small
cells when viewed in stained blood films. Erythrocytes
from members of the family Camelidae are elliptical and
not biconcave. Microcytic erythrocytes from iron-deficient
llamas exhibit irregular or eccentric areas of hypochromasia
within the cells ( Morin et al ., 1993 ).
Poikilocytosis (keratocytes and schistocytes) is often
present, being most pronounced in association with severe
microcytosis ( Harvey, 2001 ). Poikilocytosis is common in
young calves. In some cases it may result from iron deficiency,
but abnormalities in protein 4.2 in the membrane
and hemoglobin composition have also been suggested as
causative factors ( Okabe et al ., 1996 ). Folded cells and
dacryocytes are common erythrocyte shape abnormalities
in iron-deficient llamas ( Morin et al ., 1993 ).
Not only is there apparently a low incidence of this disorder
in horses and adult cats, but some cases may not be
recognized because hypochromasia is usually not apparent
when stained blood films from iron-deficient horses and
adult cats are examined. Additionally, some electronic cell
counters may not count the microcytic cells present, resulting
in a spuriously increased MCV. Electronic cell counters
with erythrocyte histogram displays provide visual
evidence that a threshold failure has occurred ( Weiser and
Kociba, 1983 ).
Increased production and release of reticulocytes from
bone marrow typically occur in response to hemorrhage
in species other than the horse. Consequently, absolute
reticulocytosis is often present in the early stage of iron
deficiency secondary to hemorrhage, at least in the dog
( Harvey et al ., 1982 ). As iron depletion becomes more
severe, there is insufficient iron for reticulocyte production,
and the absolute reticulocyte count no longer increases.
Thrombocytosis is often present in animals with iron deficiency
anemia. This platelet increase may in part be related
to a stimulation of megakaryopoiesis by high erythropoietin
concentration in plasma ( Loo and Beguin, 1999 ), but
the mechanism has not been clearly defined ( Kadikoylu
et al ., 2006 ). Plasma protein concentrations may decrease
if substantial recent or ongoing hemorrhage is present.
Serum iron concentration is usually low in animals with
iron deficiency anemia ( Furugouri, 1972 ; Halvorsen and
Halvorsen, 1973 ; Harvey et al ., 1982 ; Harvey et al ., 1987a ;
Mollerberg et al ., 1975 ; Weiser and Kociba, 1983 ), but it
can also be low in association with inflammatory disorders
(Feldman et al ., 1981b ; Kolb, 1963 ; Neumann, 2003 ; Smith
and Cipriano, 1987 ; van Miert et al ., 1990 ). Serum iron is
also affected by other factors such as endogenous cortisol
concentration, administration of glucocorticoids ( Harvey
et al ., 1987b ), and consumption of meat ( Brugnara, 2003 ).
TIBC is usually normal in dogs and cats, but it is increased
in humans, rabbits, pigs, horses, and cattle ( Furugouri,
1972 ; Halvorsen and Halvorsen, 1973 ; Harvey et al ., 1982 ;
Harvey et al ., 1987a ; Mollerberg et al ., 1975 ; Weiser and
Kociba, 1983 ). However, transferrin is a negative acute
phase protein ( Ceron et al ., 2005 ), and the concomitant
presence of inflammation with iron deficiency might
lower serum TIBC concentration in animals that could
otherwise have high values.
Serum ferritin concentration correlates directly with
body iron stores in dogs, cats, horses, and pigs ( Andrews
et al ., 1994 ; Smith et al ., 1984a ; Smith et al ., 1984b ; Weeks
et al ., 1989b ). Consequently, serum ferritin is low in iron
deficiency ( Fry and Kirk, 2006 ). A problem with serum ferritin
is that it is an acute phase protein and it can increase
secondarily to inflammation or liver disease ( Ottenjann
et al ., 2006 ; Smith and Cipriano, 1987 ), resulting in an
overestimation of total body iron content that might mask
the presence of concomitant iron deficiency ( Coenen et al .,
1991 ). Suspected iron deficiency can be confirmed by finding
minimal or absent stainable iron in the bone marrow of
most species. However, stainable iron is not present in the
bone marrow of normal cats ( Harvey, 1981 ); consequently,
a lack of stainable iron does not indicate iron deficiency
in this species. Although cat bone marrow normally lacks
stainable iron (hemosiderin), it presumably still has ferritin
stores not identified using Prussian blue staining ( Blum
and Zuber, 1975 ; Navone et al ., 1988 ).
Serum soluble TfR levels and erythrocyte ZnPP concentrations
have been used in the diagnosis of iron deficiency