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

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Chapter | 3 Carbohydrate Metabolism and Its Diseases
the attendant phenomena of attempts to compensate are
exaggerated. Liver glycogen stores are depleted, but liver
glucose production continues to be increased because of
increased protein breakdown and gluconeogenesis. The
oxidation of fatty acids is accelerated and, with it, the overproduction
of the acidic ketone bodies, AcAc, 3-OH-B,
and acetone occurs. The vapor pressure of acetone (b.p.
56.5°C) is high at body temperature, and thus this volatile
compound is often detected in the breath of the severely
ketotic animal. AcAc and 3-OH-B are acidic anions, which
increase the “ anion gap ” and reduce the concentrations of
HCO 3
, Cl , Na , and K . Acidosis develops as the HCO 3
is reduced and respiratory compensation is inadequate. In
addition, there is an underutilization of ketone bodies in
starvation ( Garber et al ., 1974) and a similar underutilization
of ketone bodies occurs in diabetes ( Sherwin et al ., 1976 ).
A rapid point-of-care method for quantifying 3-OH-B
is now available and is useful in managing ketoacidosis
(Section VIII.D).
In hyperketonemia, large amounts of ketones are wasted
in the urine with the large losses of water and HCO 3
. The
acidic ketones are buffered by ammonium ions derived
from glutamine in the renal tubules, but large amounts of
ketones are ultimately lost with Na and K in the urine.
Even without ketonuria, the loss of electrolytes in the polyuria
of diabetes may be considerable. Thus, the acidosis of
the diabetic is a primary base deficit fundamentally related
to the ketonemia and to the loss of ketones and HCO 3
in
the urine.
Excess glucose in the glomerular filtrate provokes an
osmotic diuresis leading to loss of water and dehydration.
The progressively severe loss of water and electrolytes, the
dehydration, and ketoacidosis ultimately lead to collapse,
coma, and death. The condition is aggravated by renal
impairment, which fortunately is not a common finding in
diabetes of the dog. Not all the extracellular sodium deficit
is due to urinary loss, however, because as H increases,
it enters the cells. In exchange, K leaves the intracellular
compartment and some Na enters the cells. As the dehydration
progresses, extracellular K concentration may be
very high even though there may be a total body deficit.
This is an important consideration in the insulin, fluid, and
electrolyte replacement therapy of diabetic ketoacidosis.
The electrolyte replacement must include K because correction
of the acidosis and the rapid expansion of the extracellular
fluid compartment lead to the reverse exchange of
K , and this results in hypokalemia.
10 . Urinalysis
The renal threshold for glucose in the dog is about
11.1mmol/l (200mg/dl) so that the detection of even trace
amounts of glucose in the urine is an important finding
and warrants further consideration. In virtually all cases
of diabetes suspected on the basis of persistent glycosuria
alone, the diagnosis can be later confirmed. Renal diabetes
(i.e., low renal threshold for glucose) is an extremely rare
occurrence and, if it does occur, can be detected by finding
a normal blood glucose in the presence of the glucosuria.
Transient glucosurias may occur for 1 to 1½h after a heavy
carbohydrate meal, but a 2-h postprandial glucosuria is a
strong indication of diabetes.
Currently, detection of glucosuria using the urinalysis
sticks is the most common method of point-of-care evaluation
of the clinical success of insulin therapy. There are
disadvantages to this system because of owner difficulties,
inconsistencies, and inaccuracies. The FrAm method,
whereby only biweekly blood samplings need be taken,
can have decided advantages in following the course of
insulin therapy.
An elevated urinary specific gravity (SG) has in the
past been considered to be a good indicator of glucosuria
and, hence, of diabetes. SG is a measure of the concentration
of solutes in the urine, principally the cations (Na ,
K , NH 4
), anions (PO 4
, SO 4
, HCO 3 , Cl ), and urea. The
observed SG of urine is the result of the additive effect of
the contributions of all these solutes. It is for this reason
that the osmolality of any fluid, urine or plasma, can be
estimated by simply adding up the major anions and cations
expressed in mmols/l (see the chapter on acid-base).
Albumin in urine increases the SG by 0.003 units for each
10g/l (1g/dl), whereas glucose increases it by 0.004 units
for each 55mmol/l (1g/dl). Even though the presence
of glucose does increase the SG linearly, a 4 reaction,
140mmol/l (2.5g/dl) would increase the SG by only 0.010
unit, an insignificant value on the refractometer. Therefore,
although SG is a valuable measure of renal function, it is
of no value with respect to the glucosuria of diabetes or to
proteinuria. Conversely, by subtracting the contributions of
protein and glucose from the observed SG, a more accurate
measure of renal function in diabetes may be obtained.
Proteinuria is a common sign of renal disease and is
often observed in diabetes in dogs. There is doubt whether
this is associated with chronic nephritis or whether it is due
to renal failure as an aftermath of diabetes.
Diabetic nephropathies resulting from microangiopathies
of the glomerular tufts and basement membrane injuries
are frequent and serious complications of the chronic,
poorly controlled, human diabetic. A degree of renal arteriosclerosis
is common in diabetic dogs, but this lesion is
not comparable to the Kimmelstiel-Wilson lesion seen in
humans. Also, only 1 of 10 diabetic dogs at necropsy had
a significant renal lesion although most had some degree
of nephritis ( Cotton et al ., 1971 ). In renal function studies
of experimental streptozotocin diabetes ( Kaneko et al .,
1978b ) and in spontaneous diabetes ( Kaneko et al ., 1979 ),
the urea, creatinine, and phosphate clearances were normal.
The blood urea and creatinine concentrations were only
slightly elevated, and it was concluded that renal disease is
not a significant complication in the dog.