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

III. Neurohypophysis
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in domestic animals. Deficient VP release causes the syndrome
of diabetes insipidus, which is characterized by insatiable
polydipsia and persistent inappropriately dilute urine
in the presence of strong osmotic stimuli for VP release. The
disease is not uncommon in the dog and cat ( Feldman and
Nelson, 2004 ; Rijnberk, 1996 ) and rare in other species.
VP excess is known as the syndrome of inappropriate
ADH (SIADH) secretion or the Schwartz-Bartter syndrome.
The VP release is inappropriately high in relation to the
plasma osmolality. The resulting defect in water excretion
causes hyponatremia, which is the hallmark of SIADH.
This condition has been documented as a disease of the dog
and at the same time studies of the threshold and sensitivity
of VP secretion revealed that it occurred in two forms
(Houston et al. , 1989 ; Rijnberk et al. , 1988a ). The polyuria
can be explained by down-regulation of V2 renal receptors
resulting from chronic exposure of the kidney to increased
VP levels ( Rijnberk, 1996 ; Rijnberk et al. , 1988a ).
In dogs with primary polydipsia, described as a psychological
problem, evidence indicates a primary disturbance
in the regulation of VP secretion ( van Vonderen
et al. , 1999) and a wide variation in VP responses to hypertonic
stimulation can be found, including a hyperresponse,
a hyporesponse, and a nonlinear response ( van Vonderen
et al. , 2004a ).
The glucocorticoid excess in Cushing’s syndrome
is accompanied by (mild) polyuria in the dog. A marked
impairment of the osmolality-regulated VP release at the
pituitary level may, in concert with a partial VP resistance
at the kidney level, be the cause of the corticosteroidinduced
polyuria ( Biewenga et al. , 1991 ). Chronic liver
disease is accompanied by both enhanced activity of the
pituitary-adrenocortical axis and disturbances in sodium
and water homeostasis. Also in these cases, a profoundly
impaired osmoregulation of VP release was found
( Rothuizen et al. , 1995 ). Besides hyperadrenocorticism
and hepatic failure, other conditions in the dog also lead
to secondary or acquired nephrogenic diabetes insipidus.
Hypercalcemia ( Rijnberk, 1996 ), pyometra ( Heiene et al. ,
2004 ), and hyperaldosteronism ( Rijnberk et al. , 2001 ) that
are marked by polyuria and polydipsia are associated with
impaired renal response to VP, either by VP receptor resistance
or down-regulation of AQP2.
In dogs with secondary polycythemia, blood hyperviscosity
and increased blood volume result in impaired VP
release and polyuria ( van Vonderen et al. , 1997b ). In dogs
with spontaneous pericardial effusion, moderately elevated
plasma VP levels declined rapidly after pericardiocentesis
( Stokhof et al. , 1994 ).
6 . Tests
The diagnosis of VP deficiency requires that it be differentiated
from other causes of water diuresis. Following
exclusion of conditions such as hyperadrenocorticism,
hyperthyroidism, and hypercalcemia, both nephrogenic
diabetes insipidus and primary polydipsia remain
as the main differential diagnoses. Urine-specific gravity
(Usg) and urine osmolality (Uosm) are used routinely
in the dog to assess renal concentrating ability. However,
intra- and interindividual variations of these parameters
in healthy dogs are much larger than previously thought
( van Vonderen et al. , 1997a ), which complicates the interpretation
of findings in pathological conditions. Slightly
elevated plasma osmolality may suggest neurogenic or
nephrogenic diabetes insipidus, whereas low plasma osmolality
may be observed in primary polydipsia. However, in
many cases this parameter is not conclusive.
The procedure that is widely used to differentiate these
disorders is the modified water-deprivation test, as introduced
for the dog by Mulnix et al. (1976 ). In this test
maximal urine concentration is induced by several hours of
dehydration. Once a plateau in urine osmolality is reached,
the effect of an injection with VP is investigated. A further
increase in urine osmolality by 50% or more is regarded as
diagnostic for VP deficiency.
Although these indirect criteria for VP secretion can usually
differentiate between complete neurogenic and complete
nephrogenic diabetes insipidus, they cannot differentiate
among partial neurogenic, partial nephrogenic, and dipsogenic
polyurias. In these situations, direct measurements of
plasma VP during hypertonic saline infusion are required
(Biewenga et al. , 1989 ). However, the significance of the VP
response to hypertonic saline infusion as the gold standard for
diagnosis of canine polyuria is complicated by the occurrence
in healthy dogs of spontaneous VP pulses and increased VP
pulses (to the magnitude of “ erratic bursts ” ) during hypertonic
saline infusion ( van Vonderen et al. , 2004b ).
Hypersecretion of VP can only be diagnosed by measurements
of the circulating concentrations of the hormone
( Table 18-8 ). The basic criterion is the presence of
“ inappropriately ” high VP concentrations in relation to the
hypoosmolality of the extracellular fluid. The type of the
osmoregulatory defect can best be judged by repeatedly
measuring plasma osmolality and VP during administration
of hypertonic saline ( Rijnberk et al. , 1988a ). Details
of this test are given in Section IV.
Measurement of urinary excretion of AQP2 may
become a diagnostic tool in dogs for differentiation of
polyuric conditions such as (partial) central or nephrogenic
diabetes insipidus, primary polydipsia, and inappropriate
VP release ( van Vonderen et al. , 2004c ).
B . Oxytocin
1. Gene Expression
The oxytocin (OT) gene expression is predominantly found
in the hypothalamic supraoptic nucleus and paraventricular
nucleus ( Burbach et al. , 1986 ). The neurons project