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

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Chapter | 7 The Erythrocyte: Physiology, Metabolism, and Biochemical Disorders
Laboratory findings in these horses were similar to
those from two related trotter mares that were reported to
have persistent hemolytic anemia, methemoglobinemia, GR
deficiency, and decreased GSH concentrations within RBCs
( Dixon and McPherson, 1977 ). However, the GR deficiency
did not appear to result from FAD deficiency, and the Cb 5 R
activity was reportedly normal.
6 . Gamma-Glutamylcysteine Synthetase Defi ciency in
Sheep
An autosomal dominant inherited deficiency in RBC GSH
in Corriedale and Merino sheep results from low levels
of gamma-glutamylcysteine synthetase (GCS), the first
enzyme involved in GSH synthesis ( Fisher et al. , 1986 ;
Smith et al. , 1973 ). Although the specific activity of the
enzyme is low, the molecular weight, K m values for glutamate
and cysteine, K i for GSH, and other characteristics of
purified GCS from deficient sheep are remarkably similar
to those from normal sheep ( Board et al. , 1980 ). Deficient
sheep have only about 20% to 30% of normal RBC GSH
but exhibit no clinical signs, are not anemic, and have normal
RBC life spans ( Smith et al. , 1973 ). A similar RBC
GSH-deficient syndrome has been reported in Spanish
Churra sheep ( Bayon et al. , 1994 ). Although RBCs from
these low-GSH sheep do not appear to have greater susceptibility
to injury by superoxide or hydrogen peroxide than
do RBCs from high-GSH sheep ( Eaton et al. , 1989 ), they
do exhibit greater HzB formation when exposed to acetylphenylhydrazine
in vitro ( Goto et al. , 1993 ) and kale feeding
in vivo ( Tucker et al. , 1981 ).
B . Membrane Abnormalities
1 . Hereditary Stomatocytosis in Dogs
Stomatocytes are uniconcave or cup-shaped RBCs that
have slitlike areas of central pallor on stained blood films.
Stomatocytosis is recognized in association with three different
inherited syndromes in dogs. All disorders appear
to be transmitted as autosomal recessive traits. Hereditary
stomatocytosis also consists of a heterogeneous group of
disorders in humans ( Delaunay, 2004 ).
No clinical signs occur in miniature schnauzers ( Brown
et al. , 1994b ; Giger et al. , 1988a ), standard schnauzers
(Bonfanti et al. , 2004 ), or a Pomeranian ( Harvey, 2001 ) with
stomatocytosis. Chondrodysplasia (short-limbed dwarfism)
occurs along with stomatocytosis in Alaskan malamutes
(Fletch et al. , 1975 ; Pinkerton et al. , 1974 ). This disorder is
deforming but not life threatening. The syndrome in Drentse
patrijshond dogs has been termed familial stomatocytosishypertrophic
gastritis (Slappendel et al. , 1991 ). Affected
animals have polysystemic disease with growth retardation,
diarrhea, polyuria/polydipsia, hind limb weakness, pale or
icteric mucous membranes, and a somnolent mental state.
Pathological findings include hypertrophic gastritis, progressive
liver disease, polyneuropathy, and renal cysts. Affected
Drentse patrijshond dogs are usually euthanized by the time
they reach young adulthood because of a progressive deterioration
in clinical condition.
Hb values and RBC counts are low-normal or slightly
reduced, but hematocrits are normal in malamutes, schnauzers,
and Pomeranians. The MCV is increased and MCHC
decreased even though reticulocyte counts are normal or
only slightly increased. Affected Drentse patrijshond dogs
have lower hematocrits and higher reticulocyte counts
than those found in the other breeds ( Slappendel et al. ,
1991 ; Slappendel et al. , 1994 ). The MCHC is moderately
decreased, but the MCV is normal or only slightly increased.
RBCs from all breeds have increased osmotic fragility and
shortened RBC survival.
Although the specific defects are not known, the pathogenesis
of stomatocyte formation in malamutes, schnauzers,
and Pomeranians is attributed to an increase in monovalent
cations, and consequently increased water content of RBCs
caused by abnormal membrane permeability ( Giger et al. ,
1988a ; Paltrinieri et al. , 2007 ; Pinkerton et al. , 1974 ). The
swelling associated with water accumulation accounts for
the increased MCV and decreased MCHC values in affected
dogs. Stomatocytosis in these breeds resembles overhydrated
hereditary stomatocytosis in humans, a disease
characterized by a reduced or absent stomatin expression
(Fricke et al. , 2003 ). However, standard schnauzers with
hereditary stomatocytosis exhibit normal stomatin expression
( Paltrinieri et al. , 2007 ). The GSH content in affected
RBCs is about 50% to 60% of normal ( Giger et al. , 1988a ;
Harvey, 2001 ; Pinkerton et al. , 1974 ). This GSH deficiency
appears to occur from increased catabolism, but the mechanism
responsible is unknown ( Smith et al. , 1983b ).
In contrast to malamutes and schnauzers with stomatocytosis,
RBCs from affected Drentse patrijshond dogs
do not have increased total monovalent cations, and cell
water is only slightly increased; consequently, stomatocyte
formation appears to be caused by a different mechanism
(Slappendel et al. , 1994 ). The composition of phospholipids
and cholesterol in plasma and RBC membranes is abnormal
in these dogs ( Slappendel et al. , 1994 ). The authors suggest
that a defect in lipid metabolism results in altered membrane
lipid composition and a loss or contracture of membrane
components.
2 . Hereditary Elliptocytosis in Dogs
Hereditary elliptocytosis is a common disorder of RBC
shape in humans of African and Mediterranean ancestry.
There is a mechanical weakness or fragility of the RBC
membrane skeleton resulting from defects in α -spectrin,
β -spectrin, or protein 4.1 ( Gallagher, 2004 ).
Persistent elliptocytosis and microcytosis have been
described in a crossbred dog that lacked RBC membrane