The influence of Cortisol excess on kidney function in the dog

Summary

The effects of Cortisol excess on kidney function were studied in 8 normal conscious dogs. Cortisol was given orally until polyuria developed. Cortisol excess decreased urine osmolality (from 897 ± 76 to 186 ± 36 mosm. Kg^‐1) and increased urine production (from 0.7 ± 0.1 to 9.3 ± 2.4 ml kg^‐1 h^‐1).

The glomerular filtration rate increased by 23 ± 9 per cent. Sodium and potassium concentrations in plasma were decreased. 66 Per cent of the increase in urine production was due to the increase in free water clearance and 34 per cent to the increased urea excretion. Cortisol excess apparently caused polyuria by inhibition of the action of ADH in the collecting duct, resulting in a decreased water and urea reabsorption.

The decreased urea reabsorption possibly causes a smaller urea recirculation in the renal medulla and hence a decrease in concentrating capacity.     

The role of vasopressin in dogs with polyuria

Polyuria and polydipsia (PUPD) occur frequently in dogs and may be caused by a variety of endocrine, metabolic, and renal disturbances. The studies described in this PhD Thesis, which was defended in January 2004 in Utrecht, investigated the role of the antidiuretic hormone vasopressin (VP) in the pathogenesis of different forms of canine polyuria. Experiments in healthy dogs demonstrated that the ranges of urine specific gravity and urine osmolality are much larger than previously thought. A water deprivation test is not required in all polyuric dogs, because serial measurements of urine osmolality may already lead to the diagnosis of primary polydipsia, in some cases. In dogs with primary polydipsia a wide variation in VP responses to hypertonic stimulation can be found, including a hyperresponse, a hyporesponse, and a non-linear response. The significance of the VP response to hypertonic saline infusion as the 'gold standard' for a diagnosis of canine polyuria is discussed. In the dog, VP is secreted in a pulsatile fashion with a wide variation in the number of VP pulses, VP pulse duration, and VP pulse amplitude and height. The occurrence of spontaneous VP pulses may severely hamper the interpretation of the curve describing the relationship between plasma osmolality and plasma VP concentration during osmotic stimulation. A radioimmunoassay to measure the VP-dependent water channel aquaporin-2 (AQP2) in urine was developed in dogs. In healthy dogs, urinary AQP2 excretion closely reflects changes in collecting duct exposure to VP. Measurement of urinary AQP2 excretion in polyuric dogs may be helpful to distinguish between central diabetes insipidus, nephrogenic diabetes insipidus, and primary polydipsia.     

Persistent polyuria in two dogs following adrenocorticolysis for pituitary‐dependent hyperadrenocorticism

Summary

In two dogs with pituitary‐dependent hyperadrenocorticism, adrenocorticolysis with o,p'‐DDD led to the disappearance of the signs and symptoms except for the polyuria. After a modified water‐deprivation test the osmoregulation of vasopressin release was studied by hypertonic saline infusion. In both dogs the hypertonicity, thus induced, resulted in very minimal responses of the vasopressin secretion.     

Effects of dietary supplementation with a herbal extract on the performance of broilers infected with a mixture of Eimeria species

1. A herbal extract containing a blend of three essential oils, derived from oregano, laurel leaf and lavender, was investigated as a feed additive alternative to the conventional anticoccidial sodium monensin.

2. Broilers were infected with a mixture of Eimeria species or left uninfected.

Both infected and uninfected broilers were provided with diets containing either herbal extract (HEX), monensin (MON) or without these supplements (CON). The HEX group had 50?mg herbal extract/kg diet and the MON group 100?mg monensin/kg diet.

3. All of the uninfected broilers exhibited higher body weight gain and better feed conversion when compared with their infected counterparts at d 28 and 42 of age. Both HEX and MON supplements caused significant improvements in performance in the infected broilers, but failed to have any effect on uninfected broilers.

4. Faecal oocyst output measured daily by sampling excreta, and expressed on a per bird basis, was lower in the HEX and MON groups than in the CON group. However, the herbal extract was not as effective as monensin in reducing oocyst excretion. Coccidial infection caused a significant increase in total intestinal length and caecal weight, but the dietary treatments did not influence these measurements.

5. These results indicate that providing a herbal extract in the diet was not as effective as monensin in protecting broilers exposed to a coccidial challenge.     

Disturbed Vasopressin Release in 4 Dogs with So-Called Primary Polydipsia

Primary polydipsia is characterized by a marked increase in water intake and secondary polyuria, and in dogs often is described as a behavioral problem or a psychological disorder. We describe 4 dogs with primary polydipsia, diagnosed on the basis of a modified water deprivation test, in which further examination included serial measurements of urine osmolality (UOsm) and plasma vasopressin (VP) measurements during water deprivation and hypertonic saline infusion. The dogs, ranging in age from 4 months to 4 years, all were presented for evaluation of polyuria and polydipsia. Physical examination, routine blood chemistry, and urinalysis disclosed no specific cause for the polyuria and polydipsia. During serial measurements UOsm spontaneously reached high concentrations in 2 dogs, whereas in the other 2 dogs UOsm also fluctuated but on no occasion exceeded 1,000 mosm/kg. Primary polydipsia was diagnosed when UOsm exceeded 1,000 mosm/kg at the end of the modified water deprivation test and plasma osmolality did not exceed the upper limit of the reference range during testing. During water deprivation, plasma VP concentrations remained relatively low. The VP response to hypertonic saline infusion was abnormal, with an increased threshold value in 3 dogs, an increased sensitivity in 2 dogs, and an exaggerated response in 1 dog. It is concluded that some dogs fulfilling current criteria for primary polydipsia produce concentrated urine spontaneously throughout the day in a pattern similar to what has been observed in healthy pet dogs. This finding can be regarded as diagnostic and precludes the need for a water deprivation test. During water deprivation testing, all 4 dogs produced highly concentrated urine in the face of low basal plasma VP concentrations. The observed abnormal VP release in response to hypertonic stimulation may be interpreted as a primary disturbance in the regulation of VP secretion, although it might also be the result of overhydration caused by a primary abnormality in drinking behavior.     

Polyuria and Polydipsia and Disturbed Vasopressin Release in 2 Dogs With Secondary Polycythemia

In dogs, secondary polycythemia (SP) may be associated with polyuria and polydipsia (PU/PD). The pathogenesis of this PU/PD has not yet been explained. We hypothesized that hyperviscosity and increased blood volume in SP might affect vasopressin (VP) release, resulting in PU/PD. This hypothesis was tested in 2 dogs with SP caused by renal neo-plasia and PU/PD. Osmoregulation of VP release was studied by a modified water deprivation test and by investigating the VP response to hypertonic saline infusion.
Water deprivation test results were consistent with an inability to produce concentrated urine despite increasing plasma osmolality. During hypertonic saline infusion, the osmotic threshold of VP release was markedly increased in both dogs, resulting in a delayed VP response to increasing plasma osmolality. The sensitivity of VP release was low normal in both dogs. We conclude that blood hyperviscosity and increased blood volume led to impaired VP release and polyuria.     

Evaluation of canine small intestinal permeability using the lactulose/rhamnose urinary excretion test

The use of the lactulose and rhamnose urinary excretion test was evaluated in dogs with gastrointestinal disease. Lactulose and rhamnose rinary excretion was measured in three groups of dogs: clinically healthy dogs and dogs with gastrointestinal disease with and without coexistent panhypoproteinaemia. A significant increase in both the percentage of lactulose: percentage of rhamnose urinary excretion ratio and the percentage of lactulose excretion was demonstrated in dogs with hypoproteinaemia when compared to the other two groups. The results suggest that the lactulose/rhamnose urinary excretion test may prove a useful adjunct to currently available tests for assessing small intestinal function, but lacks sensitivity in detecting small intestinal mucosal damage in the absence of villus atrophy.     

Cardiac performance in conscious healthy dogs during dobutamine infusion

The aim of this study was to determine the cardiac performance of conscious healthy dogs during stimulation with dobutamine. Eight healthy unsedated beagle dogs were used. Cardiac output was measured by the thermodilution technique and blood pressures by extravascular pressure transducers. Dobutamine challenge at a dosage ranging from 275 to 50 pg kg⁻¹ min⁻¹ -1 induced a significant rise in cardiac power index ( ), cardiac index ( ), stroke index ( ) and heart rate ( ) and a significant decrease in pulmonary vascular resistance ( ) and systemic vascular resistance ( ). The highest CPI was 2·05 times greater than its basal resting value. The CI was primarily responsible for this increase in . The si and HR contributed approximately 55 per cent and 45 per cent respectively of the maximal increase in .     

The effect of a single oral dose of lysine or arginine on the excretion of free amino acids by the starved laying hen

The excretion of free amino acids by laying hens was measured during the period 0 to 5 h after the oral administration of 0.1 g lysine HCl or 0.1 g arginine HCl.

Lysine administration resulted in a significant increase in the excretion (μmoles) of arginine (6.8 to 25.9), ornithine (5.8 to 39.3) and tyrosine (3.2 to 5.1) while arginine administration resulted in a significant increase in the excretion (μmoles) of lysine (6.8 to 93.0), ornithine (4.1 to 71.9), tyrosine (2.3 to 5.5), histidine (10.8 to 88.3), threonine (16.8 to 33.3), serine (22.7 to 34.0) and glycine (17.3 to 56.3). The effect of arginine administration on lysine excretion was significantly greater than that of lysine on arginine excretion (P < 0.01).

In the lysine experiment the overall pattern of changes in the hourly excretion rate of the affected amino acids was the same as that of administered lysine. The maximum hourly excretion rate of administered arginine occurred one hour earlier than the maximum for the amino acids affected by administered arginine.

It is suggested that arginine may alleviate certain dietary amino acid excesses by increasing the excretion of that amino acid which is in excess.     

Effects of Fosinopril on Renal Function,Baroreflex Response and Noradrenaline Pressor Response in Conscious Normotensive Dogs

The blood pressure, renal function, baroreflex response of heart rate and noradrenaline (norepinephrine) pressor response were determined in conscious, normotensive, sodium-replete dogs that had received fosinopril. Oral administration of fosinopril at a dose of 1 mg/kg per day for 5 days decreased the systolic arterial pressure from 147.1±3 to 131.8±4.3 mmHg (p<0.05) and the mean arterial pressure from 99.7±3.9 to 87.5±2.8 mmHg (p<0.05), while heart rate was unchanged. A study of the noradrenaline pressor response showed a tendency to alleviate the increased MAP by fosinopril treatment, although this was not significant. There were no significant changes in the sensitivity of the baroreflex response in HR, although the setpoint was reduced. After 7 days of fosinopril treatment, the glomerular filtration rate had increased by 18.5% (p<0.05). The effective renal plasma flow tended to increase, leaving the filtration fraction unchanged. The renal vascular resistance was reduced by 11.3% (p<0.05). Fosinopril caused a significant 41.5% increase in urinary excretion of Na⁺ (p<0.05), along with an elevation of urinary excretion of K⁺ and Cl^–. It is concluded that fosinopril can lower the blood pressure, reduce the noradrenaline pressor response and lower the cardiac baroreflex setpoint to noradrenaline. Oral administration of fosinopril for 7 days affects both the renal haemodynamics and electrolyte excretions in conscious, normotensive, sodium-replete dogs.     

Adrenocortical suppression by topically applied corticosteroids in healthy dogs

Three corticosteroid products (triamcinolone acetonide, fluocinonide, betamethasone valerate) and a control product composed of water, petrolatum, mineral oil, cetyl alcohol, steryl alcohol, sodium lauryl sulfate, cholesterol, and methylparaben each were applied topically to healthy dogs (5 dogs/product) once daily for 5 consecutive days. Plasma concentrations of immunoreactive adrenocorticotropic hormone (iACTH) and cortisol were determined before 1 microgram of ACTH/kg of body weight was given intravenously (pre-ACTH values) and cortisol was again measured 60 minutes after ACTH was given (post-ACTH values). Cortisol and iACTH concentrations were determined in each dog before, during, and after administration of the corticosteroid products. All 3 corticosteroids caused prompt and sustained pituitary-adrenocortical suppression. Compared with control applications, the application of corticosteroids resulted in significant reduction of plasma cortisol and iACTH concentrations by day 2 of treatment, and the lower concentrations continued to day 5. One week after the last application of the corticosteroids, plasma iACTH concentrations in the corticosteroid-treated dogs had returned to the range of values for the control dogs; however, pre- and post-ACTH cortisol concentrations remained suppressed in all corticosteroid-treated dogs. Two weeks after the last treatment, the pre-ACTH plasma cortisol concentrations of corticosteroid-treated dogs returned to those of the control dogs, but the post-ACTH plasma cortisol concentrations remained suppressed. By 3 weeks after the last treatment, post-ACTH plasma cortisol concentrations of dogs treated with triamcinolone acetonide had returned to the range of values for the control dogs, but remained suppressed in the other 2 groups of dogs. All indices of pituitary-adrenocortical activity were within the control range by 4 weeks after the last treatment.(ABSTRACT TRUNCATED AT 250 WORDS)     

The ocular effects of intravitreal triamcinolone acetonide in dogs

The aim of the study was to determine the ocular safety of a single intravitreal dose of triamcinolone acetonide (IVTA) in dogs. Eleven healthy dogs received a single IVTA injection (8 mg) through the mid-temporal pars-plana of the left eye (OS) using a 27G needle. The dogs were re-evaluated immediately post-IVTA, every 5 min until pre-IVTA values had returned, then daily for 3 days, weekly for 1 month and monthly for 3 months. Immediately post-IVTA, all the treated eyes showed a rise in intraocular pressure (IOP) with a mean value of 41.8+/-8.9 mm Hg. The IOP values then decreased progressively to 14.5+/-2.1 mm Hg at 12.2+/-3.8 min post-IVTA. From then on, normal IOP values were maintained throughout the 3-month monitoring period. The most frequently observed clinical sign post-IVTA was conjunctival hyperaemia. The presence of triamcinolone acetonide in the vitreous was observed in all subsequent examinations of 10/11 eyes and there were still triamcinolone crystals in 5/11 eyes after 90 days. It was concluded that intravitreal injection of triamcinolone acetonide in dogs is feasible under sedation. The immediate increase in IOP post-IVTA is short-lived and pressure quickly returns to pre-IVTA levels.     

Dietary lactulose decreases apparent nitrogen absorption and increases apparent calcium and magnesium absorption in healthy dogs

To study the effect of lactulose on the route of nitrogen excretion, we fed six healthy, adult dogs on diets containing either 0, 1 or 3 g lactulose/MJ metabolizable energy according to a 3 × 3 Latin square design. The results were analysed to identify statistically significant linear trend effects of lactulose. Faecal pH was significantly lowered by lactulose. Faecal ammonium and nitrogen excretion tended to be raised by lactulose feeding whereas urinary urea excretion was significantly reduced. Lactulose feeding significantly lowered apparent nitrogen digestibility. It is concluded that lactulose feeding shifts nitrogen excretion from urine to faeces in dogs which may be beneficial for liver patients. The data are in line with the concept that lactulose stimulates bacterial growth in the colon which in turn enhances faecal nitrogen excretion and lowers the entry of colonic ammonia into the bloodstream, leading to a lesser workload for the liver and less urinary nitrogen excretion. Lactulose consumption was also found to produce a dose-dependent increase in the apparent absorption of calcium and magnesium, but not phosphorus.     

Xylazine and xylazine-ketamine in dogs

The cardiopulmonary consequences of IV administered xylazine (1.0 mg/kg) followed by ketamine (10 mg/kg) were evaluated in 12 dogs. Xylazine caused significant decreases in heart rate, cardiac output, left ventricular work, breathing rate, minute ventilation, physiologic dead space, oxygen transport, mixed venous partial pressure of oxygen, and oxygen concentration. It caused significant increases in systemic blood pressure, central venous pressure, systemic vascular resistance, tidal volume, and oxygen utilization ratio. The subsequent administration of ketamine was associated with significant increases in heart rate (transient increase), cardiac output, the alveolar-arterial PO2 gradient and venous admixture (transient increase), and arterial PCO2 (transient increase). It caused significant decreases in stroke volume (transient decrease), left ventricular stroke work (transient decrease), effective alveolar ventilation, arterial PO2 and oxygen content (transient decrease).     

Intestinal permeability testing using lactulose and rhamnose: a comparison between clinically normal cats and dogs and between dogs of different breeds

In the experiment reported here, the lactulose/rhamnose urinary excretion test was used to compare intestinal permeability between four breeds of healthy adult dogs and a group of healthy adult cats. A significant difference in permeability was found between dogs and cats (P <0.001) and between different breeds of dogs (P <0.005). The range of urinary lactulose/rhamnose ratios in the dogs in this study (0.07-0.61) was wider than previously reported (0.03-0.12). The mean value for dogs was 0.19. The range in cats was 0.41-1.25 and the mean 0.52. The results of this study suggest that breed or some other factor such as environment, diet or sexual status as well as species should be taken into account when assessing intestinal permeability using the lactulose/rhamnose urinary excretion test.     

Studies on the mechanism of polyuria induced by cortisol excess in the dog

Summary

Water balance studies were performed in 7 experimental dogs before and during a period of cortisol‐induced polyuria and in one dog with spontaneous hyperadrenocorticism before and after removal of an adrenocortical carcinoma. Measurements of urine and plasma osmolality and plasma arginine vasopressin concentration were made at regular intervals during the water deprivation studies. The results indicate that cortisol does not block the release of vasopressin but interferes with its action in the kidney.     

Cystinuria in the dog: clinical studies during 14 years of medical treatment

The purpose of this study was to summarize 14 years of clinical experience with medical treatment of 88 cystinuric dogs. Of special interest was evaluation of recurrence rate of cystine uroliths and adverse effects during long-term tiopronin treatment. Twenty-six different breeds were recognized, and the most common breeds were Dachshunds, Tibetan Spaniels, and Basset Hounds. In 76 of 88 treated dogs (86%), re-formation of cystine uroliths was prevented. Recurrence rate of cystine uroliths changed from 7 months before to 18 months during tiopronin treatment. On 28 occasions, bladder stones were found, and in about 60% of the dogs, the uroliths dissolved. Quantitative measurement of the urinary excretion of cystine showed a significantly (P < .03) higher excretion of cystine in dogs with recurrent urolith formation than in dogs with only 1 urolith episode. Another finding was a significant (P = .02) decrease in urinary cystine excretion in older (>5 years) than in younger (<5 years) dogs. Adverse effects were found in 11 dogs, and the most severe signs were aggressiveness and myopathy. All signs disappeared when tiopronin treatment was stopped. In conclusion, this study emphasizes the importance of an individual strategy for lifelong treatment of cystinuria. In addition to increasing water intake, chemical modification of the cysteine molecule into a more soluble form by means of tiopronin is useful. In dogs with re-formed cystine uroliths, dissolution may be induced by increasing the tiopronin dosage to 40 mg/kg body weight per day. In dogs with a low urolith recurrence rate and low urinary cystine excretion, the tiopronin dosage may be decreased or treatment discontinued.     

Effects of testosterone on the testes of sexually quiescent pheasants: Evidence for a negative feedback mechanism

1. The testicular response of sexually quiescent pheasants to testosterone was studied by injection of testosterone alone and in combination with chicken pituitary extract (CPE) for 20 d.

2. Testosterone alone caused a significant decrease in testicular weight, whereas CPE alone caused a significant increase. In combination testosterone and CPE caused no significant change in testicular weight, suggesting a suppression of the stimulatory effect of CPE by testosterone. The depressive effect of testosterone on testicular weight may be explained on the basis of negative feedback mechanism.

3. CPE alone stimulated the production of spermatogonia and primary spermatocytes whereas testosterone, alone or with CPE, did not elicit such a response. The lack of response of the germinal epithelium to testosterone may indicate the ineffectiveness of the hormone in initiating spermatogenesis in pheasants.     

Assessment of lithium dilution cardiac output as a technique for measurement of cardiac output in dogs

OBJECTIVES: To determine agreement of cardiac output measured by use of lithium dilution cardiac output (LiDCO) and thermodilution cardiac output (TDCO) techniques in dogs and to determine agreement of low- and high-dose LiDCO with TDCO. ANIMALS: 10 dogs (7 males, 3 females). PROCEDURE: Cardiac output was measured in anesthetized dogs by use of LiDCO and TDCO techniques. Four rates of cardiac output were induced by occlusion of the caudal vena cava, changes in depth of anesthesia, or administration of dobutamine. Lithium dilution cardiac output was performed, using 2 doses of lithium chloride (low and high dose). Each rate of cardiac output allowed 4 comparisons between LiDCO and TDCO. RESULTS: 160 comparisons were determined of which 68 were excluded. The remaining 92 comparisons had values ranging from 1.10 to 12.80 L/min. Intraclass correlation coefficient (ICC) between low-dose LiDCO and TDCO was 0.9898 and between high-dose LiDCO and TDCO was 0.9896. When all LiDCO determinations were pooled, ICC was 0.9894. For determinations of cardiac output < 5.0 L/min, ICC was 0.9730. Mean +/- SD of the differences of TDCO minus LiDCO for all measurements was -0.084+/-0.465 L/min, and mean of TDCO minus LiDCO for cardiac outputs < 5.0 L/min was -0.002+/-0.245 L/min. CONCLUSIONS AND CLINICAL RELEVANCE: The LiDCO technique is a suitable substitute for TDCO to measure cardiac output in dogs. Use of LiDCO eliminates the need for catheterization of a pulmonary artery and could increase use of cardiac output monitoring, which may improve management of cardiovascularly unstable animals.     

Nephrogenic diabetes insipidus in a 14-year-old gelding

Abstract

CASE HISTORY: A 14-year-old Cleveland Bay cross gelding was presented with severe urinary incontinence that had been present for 1 year, and chronic polydipsia and polyuria over 4 years. Water intake had been recorded as 240 L over a 24-hour period.

CLINICAL FINDINGS: The horse had marked urinary incontinence and polyuria and polydipsia. The urine was markedly hyposthenuric, but no abnormalities on urinalysis were detected. There were no other abnormal clinical or neurological signs. Haematological and serum biochemical examinations showed no abnormalities and ultrasonographic and endoscopic examination of the urinary tract did not reveal any abnormalities. The horse underwent a modified water deprivation test and failed to concentrate its urine after 5 days. 1-desamino-8-d-arginine vasopressin (DDAVP) was administered I/V but the urine remained isosthenuric with a specific gravity of 1.010.

DIAGNOSIS: Nephrogenic diabetes insipidus. A definitive cause of the urinary incontinence was not found but overflow incontinence was considered a possibility.

CLINICAL RELEVENCE: Despite being a rare condition in the horse diabetes insipidus should be considered in cases of severe polydipsia and polyuria in mature horses.