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

X. Disorders of Ruminants Associated with Hypoglycemia
75
muscle, and type VIII is deficient in leukocyte or hepatic
phosphorylase b kinase (PBK). This disease is uniquely
sex linked.
Of these 11 types in humans, only types I, II, III, and
VIII are found in animals. Other forms of glycogen storage
in animals are described as GSD-like based on their pathological
patterns of glycogen accumulation. GSD in animals
has been reviewed by Walvoort (1983) .
There is an inherited PFK deficiency in the springer
spaniel dog, but unlike human type VII GSD, there is no
muscle pathology or glycogen accumulation in muscle.
The deficiency in the dog is expressed as a hemolytic anemia
caused by a deficiency of the PFK isoenzyme in the
erythrocytes and is rightly considered to be an inherited
erythrocyte enzyme deficiency rather than a GSD ( Giger
et al ., 1985 ). Mammalian PFK is present in tissues as tetramers
composed of combinations of three different subunits:
PFK-M (muscle), PFK-L (liver), and PFK-P (platelets).
Human and dog muscle and liver have homogenous tetrameric
PFK-M4 and PFK-L4, respectively. Human erythrocyte
PFK is a mixed tetramer, PFK-L2/PFK-M2, whereas
the dog erythrocyte PFK is a mixed tetramer, PFK-M2/
PFK-P2 ( Vora et al ., 1985 ). In PFK-M subunit deficiency
in the dog erythrocyte, PFK-L replaces PFK-M; PFK-L2/
PFK-P2. In the human erythrocyte, PFK-P replaces PFK-M;
PFK-L2/PFK-P2. Although the substituted PFK in the
erythrocyte is the same in dog or human, the deficiency in
the human is expressed as a GSD, whereas in the dog it is
expressed as an exertional hemolytic anemia. The anemia
occurs after heavy exertional respiratory stress as in vigorous
hunting or exercise. Hyperventilation induces a respiratory
alkalosis, which in turn increases the fragility of the
erythrocyte and the hemolytic anemia occurs ( Giger et al .,
1985 ).
A radiation induced type I GSD occurs as an autosomal
recessive condition in the C3H mouse and is characterized
by hypoglycemia, early death, and a deficiency of liver
G-6-Pase (Gluecksohn-Welch, 1979).
Type II GSD has been described in Brahman cattle
( O’Sullivan et al ., 1981 ), the Lapland dog ( Walvoort et al .,
1982 ), and the Japanese quail ( Murakami et al ., 1980 ). In
the Brahman cattle, type II is characterized by early death,
generalized glycogen deposition, and a marked decrease in
AAGase activity. It is inherited as an autosomal recessive.
In the Lapland dog, there is also early death, generalized
glycogen deposition, hepatomegaly, and cardiomegaly.
There is also a marked decrease in heart and liver AAGase.
The Japanese quail with type II is also characterized by
early death; glycogen deposition in the heart, liver, and
muscles; and decreased AAGase.
Type III occurs in the German Shepherd dog and is characterized
by early death, little or no response to epinephrine
or glucagon, hepatomegaly, and cardiomegaly with glycogen
accumulation. The glycogen has a limit dextrin structure,
and there is a very low debrancher enzyme activity in
liver and muscle ( Ceh et al ., 1976 ; Rafaguzzaman et al .,
1976 ).
Type VIII is seen in the rat and the mouse. In the rat,
the disease is inherited as an autosomal recessive, it appears
healthy but is hypoglycemic, has hepatomegaly because
of glycogen accumulation in the liver, and has a very low
liver phosphorylase kinase activity ( Clark et al ., 1980 ).
The affected mouse is apparently healthy but has increased
glycogen accumulation in the muscle with a very low muscle
PBK. The inheritance is sex linked ( Gross, 1975 ).
X . DISORDERS OF RUMINANTS
ASSOCIATED WITH HYPOGLYCEMIA
A . General
The principal disorders of domestic ruminants in which
hypoglycemia is a salient feature are bovine ketosis and
ovine pregnancy toxemia. Pregnancy toxemia characteristically
is a widespread disease of high mortality occurring
in the pregnant ewe just before term, the time when
carbohydrate demands are highest, especially in those
ewes carrying more than one fetus. Bovine ketosis, on the
other hand, occurs in the high producing dairy cow, characteristically
during the early stages of lactation when milk
production is generally the highest. Abnormally high levels
of the ketone bodies, acetone, AcAc, 3-OH-B, and isopropanol
appear in blood, urine, and in the milk. The clinical
signs of ketosis accompany these alterations: loss of appetite,
weight loss, decrease in milk production, and nervous
disturbances.
The energy metabolism of the ruminant is focused on
the utilization of the volatile fatty acids produced by rumen
fermentation rather than on carbohydrates as in the nonruminant.
The carbohydrate economy of the ruminant is significantly
different from that of the nonruminant, and an
appreciation of these differences is important to the understanding
of these metabolic disorders of the ruminant.
B . Carbohydrate Balance
1 . Glucose Requirements
The heavy demands for glucose in early lactation and in
late pregnancy are well known. Kleiber (1959) calculated
that about 60% of the lactating cow’s daily glucose requirement
is for the production of milk. The balance sheet
( Table 3-10 ) indicates a total daily glucose requirement of
1140g of which 700 g appear in the milk. For sheep in late
pregnancy, the fetus utilizes about one-third to one-half of
the daily glucose turnover of 100g.
A good approach to assess the glucose requirements
of an animal is to measure its turnover rate or the rate at
which glucose enters or leaves the circulation. This is best