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

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Chapter | 3 Carbohydrate Metabolism and Its Diseases
is on a standard carbohydrate diet for 3 days; (2) the intravenous
test is used, and, most important; (3) blood sampling
is continued for 6 to 8 hours. A prolongation of the
hypoglycemic phase (phase III, Fig. 3-12 ) is the most significant
portion of the curve.
A dog with a tendency toward persistent hypoglycemia
is likely to have an abnormal response in the insulin tolerance
test, but this is not a reliable test of insulinoma. The
tolerance curve may have a minimal drop in blood glucose
and remain below the original level for a prolonged length
of time. Therefore, the curve has “ insulin resistance ” and
“ hypoglycemia unresponsiveness. ” Use of this test carries
some risk for a hypoglycemic crisis, so a glucose solution
for intravenous administration should be at hand. Similarly,
the glucagon stimulation test has not been a reliable test for
hyperinsulinism.
The hypoglycemia that follows oral administration of
leucine in children has been used in human patients with
islet cell tumors. Marked hypoglycemia occurs within 30
to 60 min after L-leucine administration. Leucine-induced
hypoglycemia is also associated with a rise in plasma insulin.
In patients with islet cell tumors, leucine sensitivity
disappeared after surgical excision of the tumor, which indicates
that the tumorous islet cells alone were being stimulated
by the leucine. This test has been used successfully
in pancreatic islet cell tumors of dogs.
Currently, the most useful tests are the serum insulin
and the fasting plasma glucose taken as described earlier.
There is an inappropriately high level of insulin ( 20 μ U/l)
with a hypoglycemia of 3mmol/l ( 55mg/dl).
C . Hypoglycemia of Baby Pigs
Hypoglycemia of baby pigs occurs during the first few
days of life and is characterized by hypoglycemias of
2.2 mmol/l ( 40 mg/dl), apathy, weakness, convulsions,
coma, and finally death.
The newborn baby pig is particularly susceptible to hypoglycemia.
At birth, the blood glucose level is 6 mmol/l
( 110 mg/dl) and, unless the pig is fed or suckles shortly
after birth, its blood glucose drops rapidly to hypoglycemic
levels within 24 to 36 hours. The liver glycogen, which is
high (14.8%) at birth, is almost totally absent at death. In
contrast, newborn lambs, calves, and foals are able to resist
starvation hypoglycemia for more than a week. If the baby
pig suckles, its ability to withstand starvation progressively
increases from the day of birth. A 10-day-old baby pig can
be starved up to 3 weeks before symptoms of hypoglycemia
occur.
Gluconeogenic mechanisms are undeveloped in the
newborn pig, which indicates that the gluconeogenic
enzymes of the baby pig are inadequate at birth. This also
indicates that these enzymes need to be induced by feeding
so they can reach their maximal activities within 1 or
2 weeks after birth. The precise hepatic gluconeogenic
enzymes and their inducibility by feeding have not yet
been identified.
The association of baby pig hypoglycemia with complete
or partial starvation is shown by the findings that
their stomachs are empty at necropsy, and the syndrome
itself is indistinguishable from experimental starvation of
the newborn baby pig. Starvation of the newborn pig under
natural conditions can occur because of factors relating
to the sow (agalactia, metritis, etc.) or to the health of the
baby pig (anemia, infections, etc.), either case resulting
in inadequate food intake. The requirement for feeding to
induce the hepatic gluconeogenic mechanisms in the newborn
baby pig explains its inability to withstand starvation
in contrast to the newborn lamb, calf, or foal, which is born
with fully functioning hepatic gluconeogenesis.
D . Glycogen Storage Diseases
The glycogen storage diseases (GSD) are characterized
by the pathological accumulation of glycogen in tissues.
Based on their patterns of glycogen accumulation, their
clinical pathological findings, their enzymes of glycogen
metabolism, and the structural analyses of their glycogen,
the GSDs in humans have been classified into types
I through X and 0 and into their various subtypes ( Shin,
2006 ). All have an autosomal recessive mode of inheritance
except for GSD VIII, which is sex linked. Their glycogen
structures are normal except in types III and IV.
Type I or classical von Gierke’s disease is characterized
by increased liver glycogen leading to a marked hepatomegaly.
There is a marked hypoglycemia and the blood
glucose response to epinephrine or glucagon is minimal or
absent. The liver glycogen structure is normal. The defect
in this disease is a deficiency of the enzyme G-6-Pase.
Type II or Pompe’s disease is a generalized glycogenosis
with lysosomal accumulation of glycogen and early
death. The defect in this disease is a deficiency of acidα
-glucosidase (AAGase). In type III or Cori’s disease, the
debrancher enzyme is deficient, which leads to the accumulation
of glycogen of abnormal structure. The branches
are abnormally short, and there are an increased number of
branch points; it is a limit dextrin, and the disease is sometimes
called a limit dextrinosis. There is a variable hypoglycemia,
little or no response to epinephrine or glucagon,
hepatomegaly, cardiomegaly, and early death. In type IV
or Andersen’s disease, the brancher enzyme is deficient,
which leads to a glycogen with abnormally long branches
and few branch points. It is clinically similar to type III.
In type V or McArdle’s disease, muscle phosphorylase
(MPase) is deficient, whereas in type VI, it is liver phosphorylase
(LPase) that is deficient. Type VII or Tarui’s
disease is characterized by a deficiency of muscle phosphofructokinase
(PFK) with accumulation of glycogen in