Portosystemic shunts (PSS) provide a direct vascular connection from the portal vein to the systemic circulation, so that substances in the portal blood are diverted from the intestinal tract to bypass the liver without hepatic metabolism. Dogs with pSS are very likely to develop ammonium urate uroliths. These uroliths occur in both males and females and are usually, but not always, diagnosed in animals over 3 years of age. The predisposition of dogs with pSS to urate urolithiasis is associated with concomitant hyperuricemia, hyperammonemia, hyperuricuria and hyperammoniuria.
However, not all dogs with pSS have ammonium urate uroliths.
Etiology and pathogenesis
Uric acid is one of several breakdown products of purine. In most dogs it is converted by hepatic urease to allantoin. (Bartgesetal., 1992). However, in pSS, little or no uric acid produced from purine metabolism passes through the liver. Consequently, it is not completely converted to allantoin, resulting in an abnormal increase in serum uric acid concentration. When examining 15 dogs with pSS at the University of Minnesota teaching hospital, the serum uric acid concentration was determined to be 1.2-4 mg/dL; in healthy dogs, this concentration was 0.2-0.4 mg/dL (Lulichetal., 1995). Uric acid is freely filtered by the glomeruli, reabsorbed in the proximal tubules and secreted into the tubular lumen of the distal proximal nephrons.
Thus, the concentration of uric acid in urine is determined in part by its concentration in serum. Due to northosystemic blood shunting, the concentration of uric acid in the serum increases, and, accordingly. in urine. The uroliths that form in pSS usually consist of ammonium urates. Ammonium urates are formed because the urine becomes supersaturated with ammonia and uric acid due to the diversion of blood from the portal system directly into the systemic circulation.
Ammonia is produced mainly by bacterial colonies and is absorbed into the portal circulation. In healthy animals, ammonia enters the liver, and there it is converted into urea. In dogs with pSS, a small amount of ammonia is converted to urea, so its concentration in the systemic circulation increases. Increased concentrations of circulating ammonia result in increased urinary ammonia excretion. The result of portal blood bypass of hepatic metabolism is an increase in systemic concentrations of uric acid and ammonia, which are excreted in the urine. If the saturation of urine with ammonia and uric acid exceeds the solubility of ammonium urates, they precipitate. Precipitation under conditions of supersaturated urine leads to the formation of ammonium urate uroliths.
Clinical symptoms
Urate uroliths in pSS usually form in the bladder, therefore, affected animals will develop symptoms of urinary tract disease - hematuria, dysuria, pollakiuria and urinary dysfunction. With urethral obstruction, symptoms of anuria and post-nasal azotemia are observed. Some dogs with bladder stones do not have symptoms of urinary tract disease. Despite the fact that ammonium urate uroliths can also form in the renal pelvis, they are found there very rarely. The PSS dog may have symptoms of hepatoencephalopathy - tremors, drooling, seizures, bleeding and slow growth
Diagnostics
Rice. 1. Microphotograph of urine sediment from a 6-year-old male miniature schnauzer. Urine sediment contains crystals of ammonium urate (unstained, magnification x 100)
Rice. 2. Double contrast cystogram
ma of a 2-year-old male Lhasa Apso with PSS.
Three radiolucent concretions are shown.
ment and a decrease in liver size. At
analysis of stones removed by surgery
chemically, it was revealed that they are
100% consisted of ammonium urate
Lab tests
Ammonium urate crystalluria is often found in dogs with pSS (Figure 1), which is an indicator of possible stone formation. Urine specific gravity may be low due to decreased concentration of urine in the nocturnal medulla. Another common disorder in dogs with pSS is microcytic anemia. Serum chemistry tests in dogs with pSS are generally normal, except for low blood urea nitrogen concentrations caused by insufficient conversion of ammonia to urea.
Sometimes there is an increase in the activity of alkaline phosphatase and alanine aminotransferase, and the concentration of albumin and glucose may be low. Serum uric acid concentrations will be elevated, but these values should be interpreted with caution due to the unreliability of spectrophotometric methods for uric acid analysis. (Felicee et al., 1990). In dogs with pSS, liver function test results will include increased serum bile acid concentrations before and after feeding, increased blood and plasma ammonia concentrations before and after ammonium chloride administration, and increased bromsulfalein retention.
X-ray studies
Ammonium urate uroliths may be radiolucent. therefore, sometimes they cannot be identified on regular x-rays. However, an X-ray of the abdominal cavity can show a decrease in the size of the liver due to its atrophy, which was the result of portosystemic shunting of the blood. Rsnomegaly is sometimes observed in pSS; its significance is unclear. Ammonium urate uroliths in the bladder can be seen with double-contrast cystography (Figure 2) or ultrasound. If uroliths are present in the urethra, then contrast retrography is necessary to determine their size, number and location. When assessing the urinary tract, double contrast cystography and retrograde contrast urethrography have several advantages over abdominal ultrasound. Contrast images show both the bladder and urethra, but ultrasound scans show only the bladder. The number and size of stones can also be determined by contrast cystography. The main disadvantage of contrast radiography of the urinary tract is its invasiveness, since this examination requires sedation or general anesthesia. The condition of the kidneys can be assessed in terms of the presence of stones in the renal pelvis, but excretory urography is a more reliable way to examine the kidneys and ureters.
Treatment
Although it is possible to medically dissolve ammonium urate uroliths in dogs without pSS using an alkaline low-purine diet in combination with allonurinol, drug therapy will not be effective in dissolving stones in dogs with pSS. The effectiveness of allopurinol may be altered in these animals due to the biotransformation of the short half-life drug to the long half-life oxypurinol. (Bartgesetal.,1997). Also, drug dissolution may be ineffective if uroliths contain other minerals in addition to ammonium urates. In addition, when allopurinol is prescribed, xanthine may be formed, which will interfere with dissolution
Urate urocystoliths, which are usually small, round and smooth, can be removed from the bladder using urohydropulsion during urination. However, the success of this procedure depends on the size of the uroliths, the diameter of which should be smaller than the narrowest part of the urethra. Therefore, dogs with pSS should not undergo this type of stone removal.
Because drug dissolution is ineffective, clinically active stones must be removed surgically. Whenever possible, stones should be removed during surgical correction of pSS. If the stones are not removed at this point, then hypothetically it can be assumed that in the absence of hyperuricuria and a decrease in the concentration of ammonia in the urine after surgical correction of pSS, the stones can dissolve on their own, since they consist of ammonium urates. New research is needed to confirm or refute this hypothesis. Also, the use of an alkaline diet with low purine content may prevent the growth of existing stones or promote their dissolution after ligation of psci.
Prevention
After ligation of the PSS, ammonium urate ceases to precipitate if normal blood flow passes through the liver. However, for animals in which PSS ligation cannot be performed, or where PSS is partially ligated, there is a risk of the formation of ammonium urate uroliths. These animals require constant monitoring of urine composition to prevent the precipitation of ammonium urate crystals. In case of crystalluria, additional preventive measures must be taken. Monitoring the concentration of ammonia in the blood plasma after feeding can detect its increase, despite the absence of clinical symptoms. Measurement of serum uric acid concentration also reveals its increase. Consequently, the concentrations of ammonia and uric acid in the urine of these animals will also be increased, increasing the risk of ammonium urate uroliths. In a study at the University of Minnesota, 4 dogs with inoperable pSS were treated with an alkalinizing, low-purine diet. (PrescriptionDietCanineu/d, Hill'sPetProduct, TopekaKS), which led to a decrease in the saturation of urine with ammonium urates to a level below their precipitation. In addition, the symptoms of genatoencephalopathy disappeared. These dogs lived for 3 years without recurrence of ammonium urate uroliths.
If preventative measures are necessary, a low-protein, alkalinizing diet should be used. The use of allopurinol is not recommended for dogs with pSS.
BASIC POINTS
- Chronic renal failure (CRF) is the most commonly diagnosed kidney disease in dogs.
- Clinical signs of the disease appear only after at least 67% of the renal parenchyma ceases to function.
- Diagnosis of the early stages of renal dysfunction allows for the timely use of protection techniques, incl. transfer the animal to a special diet and prescribe appropriate drug therapy in order to slow down the development of further damage to these organs, speed up recovery time and improve the animal’s quality of life.
- The plasma clearance test for exogenous creatinine can be used in routine veterinary practice.
Chronic renal failure (CRF) is the most commonly diagnosed kidney disease in dogs. It develops as a result of the progressive and irreversible loss of functioning nephrons. Clinical signs of renal failure begin to appear when 67-75% of the renal parenchyma ceases to perform its function. Polyuria and polydipsia are usually the first signs of kidney disease, but they very often go unnoticed for a long time. It is generally accepted that a decrease in the specific gravity of urine and azotemia (i.e., the concentration of creatinine and/or urea exceeding the permissible norm) occurs only after the failure of at least 67% and 75% of the renal parenchyma, respectively (Fig. 1). Therefore, chronic renal failure is usually diagnosed at relatively late stages of kidney disease. Over the past 20 years, significant advances have been made in diet therapy and drug treatment of chronic renal failure, but the problem of its early diagnosis is still relevant. Establishing impaired renal function at the very beginning of the disease makes it possible to use means to protect these organs from further damage, incl. prescribe a special diet or drug therapy. This will slow down the development of kidney disease, shorten the recovery period and improve the quality of life of sick animals. This publication describes a number of strategic approaches to identifying renal dysfunction in dogs with subclinical ESRD.
Figure 1. Consequences of kidney disease and the development of uremic syndrome with it.
Information and training of animal owners, identification of risk factors
CRF is frequently reported in dogs. Therefore, every dog owner should be informed about chronic renal failure, its prevention, manifestations of diagnostic significance, as well as factors contributing to the development of this pathology. Particular attention should be paid to dog breeds that show a predisposition to kidney disease. It is important to reassure breeders that impaired renal function can occur even in clinically healthy dogs. Owners should be advised to regularly monitor their pets so that they can judge whether the disease is progressing or not, and promptly seek help from specialists for further examinations. Well-informed breeders can provide very important information about their pet's water and feed intake, as well as changes in animal body weight.
Risk factors associated with the development of CRF in dogs are poorly understood, but, apparently, this pathology most often manifests itself in adult animals of this species: 45% of dogs with CRF are over 10 years of age. This does not mean at all that any adult dog can get sick, but it does suggest the need to determine the concentration of creatinine in the blood plasma and specific gravity of urine (SUD) in animals as the most important indicators of the health of aging animals. Hereditary nephropathies have been reported in some dog breeds (Table 1), although their incidence remains unknown. These inherited diseases can develop in puppies, young dogs, adults and aging dogs. If you suspect that dogs of such breeds have kidney dysfunction, it is necessary to collect anamnestic data regarding whether a similar disease has occurred in animals of this line (parents, littermates, other relatives). CRF can be caused by various causes, and the establishment of any of these etiological factors (for example, according to anamnestic data that the animal has had piroplasmosis, hypertension, etc. in the past) (Fig. 2) should serve as a reason for kidney research.
Figure 2. Causes of acquired chronic renal failure
|
Table 1. List of dog breeds that haveregister hereditary nephropathy |
|
|
Disease |
Breed |
|
Amyloidosis |
Shar Pei English Fox Terrier |
|
Autosomal dominant nephropathy |
Bull Terrier |
|
Diseases accompanied by damage to the basement membrane of the kidneys |
Cocker spaniel (augosomal recessive) Doberman pinscher Samoyed husky (gender predisposition) |
|
Fanconi syndrome (renal tubular dysfunction) |
Basenji |
|
Glomerular disease |
Rottweiler |
|
Glomerulonephritis |
Bernese Mountain Dog English Spaniel |
|
Multiple cystadenocarcinoma |
German Shepherd |
|
Periglomerular fibrosis |
Norwegian Elkhound |
|
Polycystic kidney disease |
Bull Terrier Cairn Terrier West Highland White Terrier |
|
Progressive nephropathy |
Lhassa Apso and Shih Tzu |
|
Entero- and nephropathies accompanied by protein loss |
|
|
Kidney dysplasia |
Alaskan Malamug Golden Retriever Miniature Schnauzer Smooth Coated Wheaten Terrier Standard Poodle |
|
Telangiectasia |
Welsh Corgi |
|
Renal glycosuria (impaired renal tubular function) |
Norwegian Elkhound |
|
Unilateral kidney absence |
|
Regularly assess the animal's water intake, urine output, appetite and body weight
Polyuria and polydipsia, resulting from the loss of the ability to concentrate urine, are not specific to chronic renal failure, but they are considered its early clinical manifestations. It can be difficult for owners to determine the amount of urine their dogs excrete. To accurately determine this indicator, the animal is hospitalized and placed in a metabolic chamber for a day (this is usually used for experimental purposes, and not for conducting routine diagnostic examinations). Before placing the animal in the chamber and before releasing it from it, they ensure that it performs the act of urination. An adult dog excretes urine during the day in a volume approximately equal to 20-40 ml/kg of body weight (in puppies this figure is higher).
Assessing a dog's water intake is much easier, especially when the animal's access to water is controlled. Owners of dogs at high risk for chronic renal failure are recommended to monitor their pets' water consumption annually. This indicator is considered normal if it does not exceed 100 ml/kg body weight. The amount of water animals drink daily is variable, as it depends on a number of factors, including. physical activity, air temperature, type of diet, etc. Therefore, measuring the volume of water consumed by the dog is carried out for 3-4 days in a row. To avoid subjectivity when determining this indicator, the dog owner needs to weigh a bowl of water 2 times a day (with an interval of 24 hours).
A slight decrease in appetite and body weight, although not specific to chronic renal failure, often accompanies this pathology. Daily feed consumption is assessed by weighing it each time it is given to the animal. When changing the diet, the animal's appetite may change depending on how attractive the new food is to it. Weighing animals is less subjective, but this procedure should be carried out regularly and on the same scales.
Indirect assessment of renal function based on the results of repeated studies of blood plasma and urine
This article discusses the possibility of diagnosing chronic renal failure only in those animals in which this pathology is asymptomatic or manifests mild clinical signs. The best markers of kidney function in this situation are creatinine and urine specific gravity.
Plasma creatinine concentration
Creatinine is constantly formed in muscles as a result of creatine metabolism. It is excreted from the body only in the urine, being completely filtered in the kidneys through the glomeruli and only to a small extent undergoing secretion in the renal tubules. Plasma creatinine concentration is considered the best indirect indicator of renal function, although the accuracy of its determination is influenced by many factors.
In this regard, one cannot discount the influence of various factors operating before and during the analysis. Blood samples for this test should be taken from animals on an empty stomach (a 12-hour overnight fast is sufficient). Most foods contain some amount of creatinine, so after consuming them, dogs may experience an increase in its concentration in the blood above the permissible level, which causes nonspecific test readings. Physical exercise does not lead to a significant change in plasma creatinine concentration in dogs. The concentration of creatinine in the blood plasma is better determined by the enzyme method rather than the Jaffe method, since the readings of the latter are influenced by an increased (> 50 μmol/L) concentration of bilirubin in the blood.
Figure 3. The relationship between plasma creatinine concentration and glomerular filtration rate (GFR) is graphically expressed by a curved line. This indicates an early stage of renal dysfunction, manifested by a decrease in GFR and a corresponding slight change in the concentration of creatinine in the blood plasma. In contrast, in dogs with severe renal failure, significant fluctuations in plasma creatinine concentrations are noted against a background of rather limited fluctuations in GFR.
It is believed that an increase in the concentration of creatinine in the blood plasma indicates a decrease in the functional state of the kidneys. The dependence of this indicator and GFR is graphically depicted by a curve (Fig. 3). Meanwhile, the concentration of creatinine in blood plasma depends on a combination of factors such as the formation, distribution and excretion of creatinine from the body. This means that this indicator may be increased in dogs with developed muscles or those suffering from dehydration. In animals with renal failure, endogenous creatinine production is reduced (2). As a consequence, increased plasma creatinine concentrations do not necessarily correlate with GFR, since creatinine formation may also be reduced by decreased muscle mass. Dehydration can lead to a decrease in the volume of distribution of creatinine, which is dependent on the total body water supply. However, dehydration usually occurs only in the later stages of chronic kidney disease.
A once-determined concentration of creatinine in the patient’s blood plasma is usually compared with the maximum permissible value of this indicator. If the concentration of creatinine in the animal’s blood is higher than the latter, then the presence of kidney pathology is assumed, and if it is below the permissible level, then the animal is considered healthy. But in a number of situations this approach is incorrect. Literature data on the acceptable value of this indicator are very variable (Fig. 4), which is partly due to the characteristics of the dog populations in which blood testing was carried out, its dependence on age, breed and a number of other factors. In dogs of different breeds and animals of different ages, the normal concentration of creatinine in the blood is not the same. For example, it is higher in adult dogs compared to puppies, as well as in dog breeds with more developed muscles. Therefore, one should interpret very carefully a slight excess of this indicator from the norm. Impaired renal function can also occur in cases where the concentration of creatinine in the blood plasma remains within normal limits.
Figure 4. Various acceptable values for plasma creatinine t in dogs (according to veterinary guidelines or obtained from Reflotron, Kodak and Vettest analyzers). There are significant differences between data obtained from different sources, which may be due to differences in control samples or analytical methods
However, even the results of a single determination of the concentration of creatinine in the blood plasma provides valuable diagnostic information, on the basis of which the International Renal Interest Society recently proposed a classification of stages of chronic renal failure in dogs and cats based on the value of of this indicator (Table 2).
|
Table 2. ClassificationdiseaseskidneyAndrenal failuredogs (ByIRIS*) |
||||
|
Stagesdiseaseskidney Andrenalinsufficiencydogs |
||||
|
Plasma creatinine concentration (µmol/l) |
181 - 440 2.1 to 5.0 |
|||
|
"IRIS: International Renal Interest Society |
||||
A much more accurate indication is provided by serial determination of the dog's plasma creatinine concentration over a period of time (for example, one year). At the same time, it is important to standardize the testing conditions in order to ensure that to avoid the influence of factors that complicate the interpretation of the results. For example, each time blood should be taken from the dog on an empty stomach, the same testing method should be used, and the animal’s body condition should not change throughout the entire period of the study. Blood plasma samples are stored frozen until testing (at a stable temperature not exceeding -20°C). When the time comes for testing the next blood plasma sample, the one taken the previous time is thawed and examined simultaneously with the last one. This allows us to establish a “critical change” of the determined indicator, which represents the minimum difference between two successive levels of creatinine concentration in the blood plasma and reflects biologically significant changes in kidney function in healthy dogs; the “critical change” is 35 µmol/l (i.e. 0.4 mg/ dl).
If significant changes in the concentration of creatinine in the blood plasma unexpectedly appear in a dog, their connection with the animal’s health state is checked by repeated testing, which allows us to eliminate diagnostic errors (Fig. 5).
Figure 5. Dispersion of creatinine content in blood plasma due to analytical errors. Dog plasma samples were tested twice in a blinded manner in the same laboratory. Very large discrepancies in the results of testing one sample were obtained - 0.7 (62 µmol/l) and 2.1 mg/dl (186 µmol/l). These observations indicate the need to retest serum samples when unexpectedly high or low readings are obtained compared to previous plasma results from the same animal.
Urine Specific Gravity (USG)
UMR is the ratio of the mass of a certain volume of urine to the mass of the same volume of clean water at the same temperature. SLM is determined using a refractometer. Changes can occur already at the initial stage of renal failure. However, BMR, which is highly variable even in healthy dogs, can vary depending on the animal's water consumption and diet. The SPM also varies from day to day, from one sample to the next. With normal body hydration, the BMR usually ranges from 1.015 to 1.045, but can decrease to 1.001 or increase to 1.075. If the BMR rises above the level of 1.030, the dog begins to actively reabsorb water from the renal tubules and collecting ducts of the kidneys. When the SMR decreases below 1.008, the animal begins to resorption of salts from the filtrate located in the renal tubules. In both cases, the kidneys compensate for the mentioned changes. When determining the SMR, the degree of hydration of the animal’s body is taken into account: the SMR is too low (<1,030) на фоне обезвоживания организма указывает на первичную дисфункцию почек или другие причины, повлекшие за собой снижение концентрирования мочи. Однако возможна и такая ситуация, когда при обезвоживании организма у собаки с субклиническим нарушением функции почек УПМ оказывается выше 1.030. Из-за вариабельности УПМ однократно выявленные изменения этого показателя не обязательно указывают на полиурию, но критериями последней служит персистентное значение УПМ в пределах от 1,008 до 1,029. Сопутствующая азотемия дает больше оснований подозревать наличие заболевания почек, но не позволяет поставить окончательный диагноз.
Other indicators
Plasma urea (or "blood urea nitrogen") concentration is also important in diagnosing clinical chronic renal failure. A number of researchers believe that this indicator correlates better with the clinical signs of the latter than the concentration of creatinine in the blood plasma. However, the concentration of creatinine in the blood plasma appears to better reflect the decrease in GFR than the urea content in the blood, which is due to the presence of many extrarenal factors that can influence the value of the latter indicator. Such factors include feeding and fasting, metabolic activity of the liver, dehydration, etc. Therefore, the concentration of creatinine in the blood plasma is of greater importance for diagnosing the early stage of renal dysfunction and the latter in subclinical cases.
Electrolyte disturbances (hyperphosphatemia, hypokalemia, hypocalcemia) are noted during periods of significant impairment of renal function, but they are absent in the early subclinical stages.
Proteinuria can develop at any stage of chronic renal failure. and its intensity is largely determined by the etiology of the disease. If proteinuria is detected, it is necessary to conduct additional studies to determine the cause of the disease. However, in many animals with chronic renal failure, proteinuria is mild.
Testing the kidneys' ability to concentrate urine
With chronic renal failure, the ability of the kidneys to concentrate urine decreases, but other factors also influence the value of the UMR, including. treatment with diuretics and glucocorticoids, glucosuria, diabetes insipidus, imbalance of basic electrolytes. A test based on limiting the dog to water allows one to evaluate the concentrating activity of the kidneys during polyuria or polydipsia without identifying their causes. It should not be used to examine dogs suffering from dehydration and/or azotemia, because its implementation in such cases is associated with the risk of harm to the health of the animals and since dehydration in patients with low BMR itself serves as confirmation of the loss of the kidneys’ ability to concentrate urine. This test can be carried out in two versions (Table 4). However, its sensitivity in diagnosing early stage chronic renal failure has not been documented.
|
Table 4. Tests, basedonlimitationgiving to an animalwater |
||
|
An approach |
Description |
|
|
Abrupt cessation of dachawater |
Conditionscarrying out |
Carrying out the test on an empty stomach is preferable. Before performing the test, the body must be sufficiently hydrated. |
|
Procedure |
1. Determination of the degree of hydration, 2. Depriving the animal of access to water. 3. Determination of the dog’s body weight, degree of hydration and BMR (4 hours after depriving the animal of access to water). |
|
|
Interpretation |
Testing is completed when: SMR becomes higher than 1.040 (this excludes chronic renal failure and diabetes insipidus, but allows for the possibility of psychogenic polydipsia); Or if the animal’s body weight decreases by more than 5% (if the BMR is below 1.030, the presence of chronic renal failure, diabetes insipidus and damage to the renal medulla are allowed; if |
|
|
Gradual deprivationdogswater |
Conditions |
Performed when the previous test does not diagnose the disease |
|
Procedure |
The animal is given water for 3 days in limited quantities. For example, first its volume is reduced to 75%, then successively by 50% and 25% compared to the initial level until its supply is stopped. The animal is then examined in the same way as during the previous test. |
|
|
Interpretation |
Same as when evaluating the results of the previous test |
|
Direct method for determining GFR
GFR is currently considered the best direct indicator of kidney function. Over the past 30 years, many new methods for determining this indicator have been proposed and tested, based on determining the clearance of certain markers in urine and blood plasma from the corresponding marker.
Urine and blood plasma clearance, limitations of use
Determination of inulin clearance in urine is considered a reference method for assessing GFR. The calculation is simple, and to carry it out you only need to know three indicators: the volume of urine excreted by the animal over a certain period, as well as the concentration of the marker in the urine and blood plasma. Despite the diagnostically valuable information provided, tests to determine urine clearance are rarely used in veterinary practice, because they are time-consuming and labor-intensive. In addition, it is necessary to collect urine at a certain time, and in the process of frequent catheterization, the risk of injury and infection of the urinary tract of animals increases. When the dog is in a metabolic chamber, urine collection can be limited to 24 hours, but it is necessary to repeatedly wash the chamber to maximize the collection of marker, the remains of which during subsequent tests may cause incorrect determination of clearance.
For these reasons, tests designed to determine plasma clearance (especially those involving a single intravenous marker) are considered an alternative to corresponding urine tests in cases where urinary excretion of the marker is negligible. The main advantage of the test, in which GFR is determined by its clearance from blood plasma after a single intravenous injection of a marker, is that only one blood sample is required to obtain the result. Radiocontrast agents (for example, iohexol and iothalamate), inulin, various radiolabeled substrates, and creatinine are used as markers. These tests have a number of limitations. For example, radiolabeled nucleotides cannot be used in routine diagnostic practice due to safety reasons and legal restrictions. Detection of most of the available markers is difficult, expensive, or simply not available in a regular veterinary clinic. The iohexol test requires a fairly large volume of blood plasma (3-4 ml, i.e. approximately 8 ml of blood), which is too much for small breed dogs. This marker is detected by a specific fluorescent glow in X-rays. Finally, determining plasma clearance, which is the ratio of the dose of a marker administered to an animal and the area under the curve of its plasma concentration (AUC) over time, requires complex calculations (data modeling using exponential equations), which discourages practicing veterinarians from its use.
Plasma clearance test for exogenous creatinine (TCPEC)
TCPEC was recently developed and tested in dogs in comparison with known methods for assessing GFR (tests to determine the clearance of inulin and endogenous creatinine in urine, blood plasma from iothalamate). Plasma and urine clearance of creatinine corresponds to GFR in dogs. With its help, it is possible to diagnose subclinical renal dysfunction in this type of animal. The main advantage of TCPEC is the ability to determine the baseline plasma creatinine concentration, which provides a direct estimate of GFR independent of the volume of distribution and endogenous production of creatinine.
Main stages of TKPEC
> Determination of the fasting baseline (initial) concentration of creatinine in the blood plasma before the test.
> Intravenous administration of a certain amount of creatinine.
> Determination of creatinine concentration in blood plasma.
Calculation of blood plasma clearance.
Main advantages of TKPEC:
> The test can be performed in routine veterinary practice because it is simple, easy to perform (intravenous marker and blood sample) and requires little time.
> To obtain a result, only 1 ml of blood is needed, which makes it possible, if necessary, to repeatedly take a blood sample from small breed dogs or puppies, and, in addition, limits the number of manipulations performed on the animal.
> Creatinine is safe: increasing its concentration in the blood plasma of dogs suffering from chronic renal failure after intravenous administration to 8000 µmol/l (90 mg/dl) does not lead to unwanted side effects.
> There is no need to resort to the services of specialized laboratories, because the concentration of creatinine in blood plasma can be quickly determined using a conventional veterinary biochemical analyzer.
> Test results are received immediately after it is administered.
> Determination of creatinine clearance does not require complex calculations
> TKPEC does not require large financial costs.
There are no commercial creatinine preparations - you have to prepare them yourself, although preparations are underway for the production of this reagent.
- The last blood sample must be taken from dogs for testing no later than 6 hours after the administration of creatinine. Therefore, the dog has to be hospitalized for the whole day during the test.
- The boundaries of normal GFR values for dogs have not been definitively determined. Currently, the maximum acceptable value for this indicator is considered to be 1.5 ml/kg/min, but the results of further studies may make adjustments.
Conclusion
The fight against chronic renal failure is one of the main problems in ensuring the health of small domestic animals. Currently, its early diagnosis is difficult, since in the initial stages of chronic renal failure it is asymptomatic. However, a number of useful actions can be taken in this direction: informing pet owners about this pathology, regular examination of their pets, including determining changes in BMR and creatinine concentration in their blood plasma over time, as well as assessing GFR (if present). this is necessary). The main hope is that early diagnosis of chronic renal failure will help timely begin to treat the sick animal and transfer it to a special diet, which will both prolong the patient’s life and improve its quality.
Gervais P. Lefebvre
Herve P. Lefebvre, DVM, PhD, Dipl ECVPT, Professor of Physiology
Jean-Pierre Bron
Jean-Pierre Braun, DVM, PhD, Dipl ECVCP, Professor of Biochemistry, Physiology and Therapeutics, Department of Pathophysiology and Experimental Toxicology, National Veterinary School of Toulouse, France
A. David J. Watson
A. David J. Watson, BVSc, PhD, FRCVS, FAAVPT, MACVSc, Dipl ECVPT,
Associate Professor of Veterinary Medicine, Faculty of Veterinary Sciences, University of Sydney, Australia
Blood chemistry.
A biochemical blood test is a laboratory diagnostic method that allows you to evaluate the functioning of many internal organs. A standard biochemical blood test includes the determination of a number of indicators that reflect the state of protein, carbohydrate, lipid and mineral metabolism, as well as the activity of some key enzymes in the blood serum.
For testing, blood is taken strictly on an empty stomach into a test tube with a coagulation activator, and the blood serum is examined.
- General biochemical parameters.
Total protein.
Total protein is the total concentration of all blood proteins. There are different classifications of plasma proteins. They are most often divided into albumin, globulins (all other plasma proteins) and fibrinogen. The concentration of total protein and albumin is determined by biochemical analysis, and the concentration of globulins by subtracting the concentration of albumin from the total protein.
Promotion:
- dehydration,
- inflammatory processes,
- tissue damage,
- diseases accompanied by activation of the immune system (autoimmune and allergic diseases, chronic infections, etc.),
- pregnancy.
False overestimation of protein can occur with lipemia (chylosis), hyperbilirubinemia, significant hemoglobinemia (hemolysis).
Demotion:
- overhydration,
- bleeding,
- nephropathy
- enteropathy,
- strong exudation,
- ascites, pleurisy,
- lack of protein in food,
- long-term chronic diseases characterized by depletion of the immune system (infections, neoplasms),
- treatment with cytostatics, immunosuppressants, glucocorticosteroids, etc.
During bleeding, the concentration of albumin and globulins decreases in parallel, however, in some disorders accompanied by protein loss, the albumin content decreases primarily, since the size of its molecules is smaller compared to other plasma proteins.
Normal value
Dog 55-75 g/l
Cat 54-79 g/l
Albumen
A homogeneous plasma protein containing a small amount of carbohydrates. An important biological function of albumin in plasma is to maintain intravascular colloid osmotic pressure, thereby preventing plasma from leaving the capillaries. Therefore, a significant decrease in albumin levels leads to the appearance of edema and effusions in the pleural or abdominal cavity. Albumin serves as a carrier molecule, transporting bilirubin, fatty acids, drugs, free cations (calcium, copper, zinc), some hormones, and various toxic agents. It also collects free radicals and binds mediators of inflammatory processes that pose a danger to tissues.
Promotion:
- dehydration
Disorders that would be accompanied by increased albumin synthesis are not known.
Demotion:
- overhydration;
- bleeding,
- nephropathy and enteropathy,
- severe exudation (for example, burns);
- chronic liver failure,
- lack of protein in food,
- malabsorption syndrome,
- insufficiency of exocrine pancreatic function
Normal value
Dog 25-39 g/l
Cat 24-38 g/l
Bilirubin.
Bilirubin is produced in macrophages by enzymatic catabolism of the heme fraction from various hemeproteins. Most of the circulating bilirubin (about 80%) is formed from “old” red blood cells. Dead “old” red blood cells are destroyed by reticuloendothelial cells. The oxidation of heme produces biliverdin, which is metabolized to bilirubin. The remaining part of circulating bilirubin (about 20%) is formed from other sources (destruction of mature red blood cells in the bone marrow containing heme, muscle myoglobin, enzymes). The bilirubin thus formed circulates in the bloodstream, being transported to the liver in the form of a soluble bilirubin-albumin complex. Bilirubin bound to albumin can be easily removed from the blood by the liver. In the liver, bilirubin binds to glucuronic acid under the influence of glucuronyltransferases. Bound bilirubin includes bilirubin monoglucuronide, which predominates in the liver, and bilirubin diglucuronide, which predominates in bile. Bound bilirubin is transported into the bile capillaries, from where it enters the bile ducts and then into the intestines. In the intestine, bound bilirubin undergoes a series of transformations to form urobilinogen and stercobilinogen. Stercobilinogen and small amounts of urobilinogen are excreted in feces. The main amount of urobilinogen is reabsorbed in the intestine, reaching the liver through the portal circulation and being re-excreted by the gallbladder.
Serum bilirubin levels rise when bilirubin production exceeds its metabolism and excretion from the body. Clinically, hyperbilirubinemia is expressed by jaundice (yellow pigmentation of the skin and sclera).
Direct bilirubin
It is conjugated bilirubin, soluble and highly reactive. An increase in the level of direct bilirubin in the blood serum is associated with reduced excretion of the conjugated pigment from the liver and biliary tract and manifests itself in the form of cholestatic or hepatocellular jaundice. A pathological increase in the level of direct bilirubin leads to the appearance of this pigment in the urine. Since indirect bilirubin is not excreted in the urine, the presence of bilirubin in the urine highlights the increase in serum levels of conjugated bilirubin.
Indirect bilirubin
The serum concentration of unconjugated bilirubin is determined by the rate at which newly synthesized bilirubin enters the blood plasma and the rate of elimination of bilirubin by the liver (hepatic bilirubin clearance).
Indirect bilirubin is calculated by calculation:
indirect bilirubin = total bilirubin - direct bilirubin.
Promotion
- accelerated destruction of red blood cells (hemolytic jaundice),
- hepatocellular disease (hepatic and extrahepatic origin).
Chylosis can cause a falsely elevated bilirubin level, which should be taken into account if a high bilirubin level is determined in a patient in the absence of jaundice. “Chylous” blood serum becomes white, which is associated with an increased concentration of chylomicrons and/or very low-density lipoproteins. Most often, chyle is the result of a recent meal, but in dogs it can be caused by diseases such as diabetes, pancreatitis, and hypothyroidism.
Demotion
No clinical significance.
Normal value:
Total bilirubin
Dog – 2.0-13.5 µmol/l
Cat – 2.0-10.0 µmol/l
Direct bilirubin
Dog – 0-5.5 µmol/l
Cat – 0-5.5 µmol/l
Alanine aminotransferase (ALT)
ALT is an endogenous enzyme from the group of transferases, widely used in medical and veterinary practice for laboratory diagnosis of liver damage. It is synthesized intracellularly, and normally only a small part of this enzyme enters the blood. If the energy metabolism of liver cells is disrupted by infectious factors (for example, viral hepatitis) or toxic, this leads to an increase in the permeability of cell membranes with the passage of cytoplasmic components into the serum (cytolysis). ALT is an indicator of cytolysis, the most studied and most indicative of even minimal liver damage. ALT is more specific for liver disorders than AST. Absolute ALT values still do not directly correlate with the severity of liver damage and with predicting the development of the pathological process, and therefore serial determinations of ALT over time are most appropriate.
Increased:
- liver damage
- use of hepatotoxic drugs
Downgraded:
- pyridoxine deficiency
- repeated hemodialysis
- sometimes during pregnancy
Normal value:
Dog 10-58 units/l
Cat 18-79 units/l
Aspartate aminotransferase (AST)
Aspartate aminotransferase (AST) is an endogenous enzyme from the group of transferases. Unlike ALT, which is found mainly in the liver, AST is present in many tissues: myocardium, liver, skeletal muscle, kidney, pancreas, brain tissue, spleen, being a less characteristic indicator of liver function. At the level of liver cells, AST isoenzymes are found both in the cytosol and in the mitochondria.
Increased:
— Toxic and viral hepatitis
— Necrosis of liver tissue
— Acute myocardial infarction
— Administration of opioids to patients with biliary tract diseases
An increase and rapid decrease suggests extrahepatic biliary obstruction.
Downgraded:
— Azotemia
Normal value:
Dog – 8-42 units/l
Cat – 9-45 units/l
An increase in ALT that exceeds an increase in AST is characteristic of liver damage; if the AST indicator increases more than the ALT increases, then this, as a rule, indicates problems with myocardial (heart muscle) cells.
γ - glutamyltransferase (GGT)
GGT is an enzyme localized on the membrane of cells of various tissues, catalyzing the reaction of transamination or transamination of amino acids in the process of their catabolism and biosynthesis. The enzyme transfers γ-glutamyl from amino acids, peptides and other substances to acceptor molecules. This reaction is reversible. Thus, GGT is involved in the transport of amino acids across the cell membrane. Therefore, the highest content of the enzyme is observed in the membrane of cells with high secretory and absorption capacity: liver tubules, bile duct epithelium, nephron tubules, small intestinal villi epithelium, pancreatic exocrine cells.
Since GGT is associated with epithelial cells of the bile duct system, it has diagnostic value in cases of liver dysfunction.
Increased:
- cholelithiasis
- in dogs with increasing concentrations of glucorticosteroids
- hyperthyroidism
- hepatitis of extra- or intrahepatic origin, liver neoplasia,
- acute pancreatitis, pancreatic cancer
- exacerbation of chronic glomerulonephritis and pyelonephritis,
Downgraded:
Normal value
Dog 0-8 units/l
Cat 0-8 units/l
Unlike ALT, which is found in the cytosol of hepatocytes and is therefore a sensitive marker of damage to cell integrity, GGT is found exclusively in mitochondria and is released only when there is significant tissue damage. Unlike in humans, anticonvulsants used in dogs do not cause an increase in GGT activity or it is minimal. In cats with liver lipidosis, ALP activity increases to a greater extent than GGT. Colostrum and breast milk contain high GGT activity in the early stages of feeding, so GGT levels are elevated in newborns.
Alkaline phosphatase.
This enzyme is found mainly in the liver (bile tubules and bile duct epithelium), kidney tubules, small intestine, bones and placenta. This is an enzyme associated with the cell membrane that catalyzes the alkaline hydrolysis of a wide variety of substances, during which the phosphoric acid residue is separated from its organic compounds.
The total activity of alkaline phosphatase in the circulating blood of healthy animals consists of the activity of liver and bone isoenzymes. The proportion of activity of bone isoenzymes is greatest in growing animals, while in adults their activity may increase with bone tumors.
Promotion:
- impaired bile flow (cholestatic hepatobiliary disease),
- nodular hyperplasia of the liver (develops with aging),
- cholestasis,
- increased osteoblast activity (at a young age),
- diseases of the skeletal system (bone tumors, osteomalacia, etc.)
— pregnancy (an increase in alkaline phosphatase during pregnancy occurs due to the placental isoenzyme).
- May be associated with hepatic lipidosis in cats.
Demotion:
- hypothyroidism,
— hypovitaminosis C.
Normal value
Dog 10-70 units/l
Cat 0-55 units/l
Alpha amylase
Amylase is a hydrolytic enzyme involved in the breakdown of carbohydrates. Amylase is produced in the salivary glands and pancreas, then enters the oral cavity or the lumen of the duodenum, respectively. Such organs as the ovaries, fallopian tubes, small and large intestines, and liver also have significantly lower amylase activity. In blood serum, pancreatic and salivary amylase isoenzymes are isolated. The enzyme is excreted by the kidneys. Therefore, an increase in serum amylase activity leads to an increase in urinary amylase activity. Amylase can form large complexes with immunoglobulins and other plasma proteins, which does not allow it to pass through the glomeruli, as a result of which its content in the serum increases, and amylase activity in the urine is normal.
Increased:
— Pancreatitis (acute, chronic, reactive).
- Neoplasms of the pancreas.
— Blockage of the pancreatic duct (tumor, stone, adhesions).
- Acute peritonitis.
— Diabetes mellitus (ketoacidosis).
— Diseases of the biliary tract (cholelithiasis, cholecystitis).
- Kidney failure.
— Traumatic lesions of the abdominal cavity.
Downgraded:
— Acute and chronic hepatitis.
- Pancreatic necrosis.
- Thyrotoxicosis.
- Myocardial infarction.
Normal values:
Dog – 300-1500 units/l
Cat – 500-1200 units/l
Pancreatic amylase.
Amylase is an enzyme that catalyzes the breakdown (hydrolysis) of complex carbohydrates (starch, glycogen and some others) into disaccharides and oligosaccharides (maltose, glucose). In animals, much of the amylase activity is due to the small intestinal mucosa and other extrapancreatic sources. With the participation of amylase in the small intestine, the process of digesting carbohydrates is completed. Various disruptions of processes in the acinar cells of the exocrine part of the pancreas, increased permeability of the pancreatic duct and premature activation of enzymes lead to “leakage” of enzymes inside the organ.
Promotion:
- kidney failure
- severe inflammatory bowel diseases (perforation of the small intestine, volvulus),
- long-term treatment with glucocorticosteroids.
Demotion :
- inflammation,
- necrosis or tumor of the pancreas.
Normal value
Dog 243.6-866.2 units/l
Cat 150.0-503.5 units/l
Glucose.
Glucose is the main source of energy in the body. As part of carbohydrates, glucose enters the body with food and is absorbed into the blood from the jejunum. It can also be synthesized by the body mainly in the liver and kidneys from non-carbohydrate components. All organs have a need for glucose, but especially a lot of glucose is used by brain tissue and red blood cells. The liver regulates blood glucose levels through glycogenesis, glycolysis, and gluconeogenesis. In the liver and muscles, glucose is stored in the form of glycogen, which is used to maintain the physiological concentration of glucose in the blood, primarily in the intervals between meals. Glucose is the only source of energy for the work of skeletal muscle under anaerobic conditions. The main hormones influencing glucose homeostasis are insulin and deregulating hormones - glucagon, catecholamines and cortisol.
Promotion:
- insulin deficiency or tissue resistance to insulin,
– pituitary tumors (common in cats),
- acute pancreatitis,
- renal failure,
- taking certain medications (glucocorticosteroids, thiazide diuretics, intravenous administration of fluids containing glucose, progestins, etc.),
- severe hypothermia.
Short-term hyperglycemia is possible with head injuries and central nervous system lesions.
Demotion:
- pancreatic tumor (insulinoma),
— hypofunction of endocrine organs (hypocortisolism);
- liver failure,
- cirrhosis of the liver;
- prolonged fasting and anorexia;
— congenital portosystemic shunts;
- idiopathic juvenile hypoglycemia in dogs of small and hunting breeds,
- insulin overdose,
- heatstroke
With prolonged contact of blood serum with red blood cells, a drop in glucose is possible, since red blood cells actively consume it, so it is advisable to centrifuge the blood as quickly as possible. The glucose level in uncentrifuged blood decreases by approximately 10% per hour.
Normal value
Dog 4.3-7.3 mmol/l
Cat 3.3-6.3 mmol/l
Creatinine
Creatine is synthesized in the liver, and after release, 98% of it enters muscle tissue, where it is phosphorylated. The resulting phosphocreatine plays an important role in storing muscle energy. When this muscle energy is needed to carry out metabolic processes, phosphocreatine is broken down into creatinine. Creatinine is a stable nitrogenous constituent of the blood, unaffected by most foods, exercise, or other biological constants, and is associated with muscle metabolism.
Impaired renal function reduces creatinine excretion, causing an increase in serum creatinine levels. Thus, creatinine concentrations approximately characterize the level of glomerular filtration. The main value of determining serum creatinine is the diagnosis of renal failure.
Serum creatinine is a more specific and sensitive indicator of renal function than urea.
Promotion:
- acute or chronic renal failure.
Caused by prerenal causes causing a decrease in glomerular filtration rate (dehydration, cardiovascular diseases, septic and traumatic shock, hypovolemia, etc.), renal associated with severe diseases of the kidney parenchyma (pyelonephritis, leptospirosis, poisoning, neoplasia, congenital disorders, trauma, ischemia) and postrenal - obstructive disorders that prevent the excretion of creatinine in the urine (obstruction of the urethra, ureter or rupture of the urinary tract).
Demotion :
- age-related decrease in muscle mass.
Normal value
Dog 26-130 µmol/l
Cat 70-165 µmol/l
Urea
Urea is formed as a result of the catabolism of amino acids from ammonia. Ammonia formed from amino acids is toxic and is converted by liver enzymes into non-toxic urea. The main part of the urea that then enters the circulatory system is easily filtered and excreted by the kidneys. Urea can also passively diffuse into the interstitial tissue of the kidneys and return to the bloodstream. Passive diffusion of urea depends on the rate of urine filtration - the higher it is (for example, after intravenous administration of diuretics), the lower the level of urea in the blood.
Promotion:
- renal failure (may be caused by prerenal, renal and postrenal disorders).
Demotion
- low intake of protein into the body,
- liver diseases.
Normal value
Dog 3.5-9.2 mmol/l
Cat 5.4-12.1 mmol/l
Uric acid
Uric acid is the end product of purine catabolism.
Uric acid is absorbed in the intestine, circulates in the blood as ionized urate, and is excreted in the urine. In most mammals, elimination is carried out by the liver. Hepatocytes, using urease, oxidize uric acid to form water-soluble allantoin, which is excreted by the kidneys. Decreased uric acid metabolism combined with decreased ammonia metabolism during portosystemic shunting leads to the formation of urate crystals with the formation of urate stones (urolithiasis).
In portosystemic shunting (PSS), uric acid formed as a result of purine metabolism practically does not pass through the liver, since PSSs represent a direct vascular connection from the portal vein to the systemic circulation, bypassing the liver.
The predisposition of dogs with pSS to urate urolithiasis is associated with concomitant hyperuricemia, hyperammonemia, hyperuricuria and hyperammoniuria. Since uric acid does not reach the liver in pSS, it is not completely converted to allantoin, which leads to a pathological increase in serum uric acid concentration. In this case, uric acid is freely filtered by the glomeruli, reabsorbed in the proximal tubules and secreted into the tubular lumen of the proximal nephrons. Thus, the concentration of uric acid in urine is determined in part by its concentration in serum.
Dalmatian Dogs are predisposed to the formation of urate crystals due to a particular metabolic disorder of the liver, leading to incomplete oxidation of uric acid.
Promotion
- uric acid diathesis
- leukemia, lymphoma
- anemia caused by vitamin B12 deficiency
- some acute infections (pneumonia, tuberculosis)
- diseases of the liver and biliary tract
- diabetes
- dermatological diseases
- kidney diseases
- acidosis
Demotion:
- diet poor in nucleic acids
- use of diuretics
Normal value
Dog<60 мкмоль/л
Cat<60 мкмоль/л
Lipase
Pancreatic lipase is an enzyme secreted in large quantities into the duodenum with pancreatic juice and catalyzing the hydrolysis of triglycerides to fatty acids and monoglycerides. Lipase activity is also observed in the stomach, liver, adipose and other tissues. Pancreatic lipase acts on the surface of lipid droplets formed in the intestine.
Promotion :
- perforation of the small intestine,
- chronic renal failure,
- use of corticosteroids,
- postoperative period
Demotion
- hemolysis.
Normal value
Dog<500 ед/л
Cat<200 ед/л
Cholesterol
Determination of cholesterol levels characterizes lipid status and metabolic disorders.
Cholesterol (cholesterol) is a secondary monohydric alcohol. Free cholesterol is a component of cell plasma membranes. Its esters predominate in blood serum. Cholesterol is a precursor to sex hormones, corticosteroids, bile acids and vitamin D. Most of the cholesterol (up to 80%) is synthesized in the liver, and the rest enters the body with products of animal origin (fatty meat, butter, eggs). Cholesterol is insoluble in water; its transport between tissues and organs occurs due to the formation of lipoprotein complexes.
With age, the level of cholesterol in the blood increases, and gender differences in concentration appear, which is associated with the action of sex hormones. Estrogens reduce, and androgens increase, total cholesterol levels.
Increased:
- hyperlipoproteinemia
— obstruction of the biliary tract: cholestasis, biliary cirrhosis;
- nephrosis;
- diseases of the pancreas;
- hypothyroidism, diabetes mellitus;
- obesity.
Downgraded:
- severe hepatocellular damage;
- hyperthyroidism;
- myeloproliferative diseases;
- steatorrhea with malabsorption;
- fasting;
- chronic anemia (megaloblastic / sideroblastic);
- inflammation, infection.
Normal value:
Dog – 3.8-7.0 mmol/l
Cat – 1.6-3.9 mmol/l
Creatine phosphokinase (CPK)
Creatine phosphokinase is an enzyme in the cytoplasm of skeletal muscle and myocardial cells that catalyzes the reversible reaction of converting creatine phosphate into creatinine in the presence of ADP, which is converted into ATP, which is the source of energy for muscle contraction.
The active form of CPK is a dimer consisting of subunits M and B, respectively, there are 3 isoenzymes of CPK: BB (found in the brain), MB (in the myocardium), and MM (in skeletal muscles and myocardium). The degree of increase depends on the nature of the damage and the initial level of the enzyme in the tissue. In cats, the content of CPK in tissues is relatively lower than in animals of other species, so in them one should pay attention to even a slight excess of the upper limit of the standard interval.
Often in cats suffering from anorexia, CPK levels may rise and fall several days after appropriate maintenance feeding.
Promotion
- damage to skeletal muscles (trauma, surgery, muscular dystrophy, polymyositis, etc.).
- after significant physical activity,
- epileptic seizures
- myocardial infarction (2-3 hours after the lesion, and after 14-30 hours it reaches a maximum, the level decreases on 2-3 days).
- metabolic disorders (phosphofructokinase deficiency in dogs, hypothyroidism, hypercortisolism, malignant hyperthermia).
When muscle tissue is damaged, along with CPK, enzymes such as LDH and AST will also increase.
Demotion:
- decrease in muscle mass
Normal value
Dog 32-220 units/l
Cat 150-350 units/l
Lactate dehydrogenase LDH
A cytosolic enzyme that catalyzes the reversible conversion of lactate to pyruvate with the participation of NADH in the process of glycolysis. With a full supply of oxygen, lactate in the blood does not accumulate, but is neutralized and eliminated. With oxygen deficiency, the enzyme tends to accumulate, causing muscle fatigue and disrupting tissue respiration. High LDH activity is inherent in many tissues. There are 5 LDH isoenzymes: 1 and 2 are present mainly in the heart muscle, erythrocytes and kidneys, 4 and 5 are localized in the liver and skeletal muscles. LDH 3 is characteristic of lung tissue. Depending on which of the five isoforms of the enzyme is found in a particular tissue, the method of glucose oxidation depends - aerobic (to CO2 and H2O) or anaerobic (to lactic acid).
Since enzyme activity is high in tissues, even relatively minor tissue damage or mild hemolysis leads to a significant increase in LDH activity in the circulating blood. It follows from this that any diseases accompanied by the destruction of cells that contain LDH isoenzymes are accompanied by an increase in its activity in the blood serum.
Promotion
- myocardial infarction,
- damage and dystrophy of skeletal muscles,
- necrotic damage to the kidneys and liver,
- cholestatic liver diseases,
- pancreatitis,
- pneumonia,
- hemolytic anemia, etc.
Demotion
Has no clinical significance.
Normal value
Dog 23-220 units/l
Cat 35-220 units/l
The degree of increase in LDH activity during myocardial infarction does not correlate with the size of the lesion in the heart muscle and can only serve as an indicative factor for prognosis of the disease. In general, being a non-specific laboratory marker, changes in LDH levels should be assessed only in combination with the values of other laboratory parameters (CPK, AST, etc.), as well as data from instrumental diagnostic methods. It is also important not to forget that even slight hemolysis of blood serum leads to a significant increase in LDH activity.
Cholinesterase ChE
Cholinesterase is an enzyme belonging to the class of hydrolases that catalyzes the breakdown of choline esters (acetylcholine, etc.) with the formation of choline and corresponding acids. There are two types of enzyme: true (acetylcholinesterase) - which plays an important role in the transmission of nerve impulses (located in nervous tissue and muscles, red blood cells), and false (pseudocholinesterase) - serum, present in the liver and pancreas, muscles, heart, brain . ChE performs a protective function in the body, in particular, it prevents the inactivation of acetylcholinesterase by hydrolyzing the inhibitor of this enzyme - butyrylcholine.
Acetylcholine serase is a strictly specific enzyme that hydrolyzes acetylcholine, which takes part in the transmission of signals through the endings of nerve cells and is one of the most important neurotransmitters in the brain. With a decrease in ChE activity, acetylcholine accumulates, which first leads to an acceleration of the conduction of nerve impulses (excitation) and then to a blocking of the transmission of nerve impulses (paralysis). This causes disorganization of all body processes, and in severe poisoning can lead to death.
Measuring the level of ChE in blood serum can be useful in case of poisoning with insecticides or various toxic compounds that inhibit the enzyme (organophosphorus, phenothiazines, fluorides, various alkaloids, etc.)
Promotion
- diabetes;
- mammary cancer;
- nephrosis;
- hypertension;
- obesity;
Demotion
- liver damage (cirrhosis, metastatic liver disease)
- muscular dystrophy, dermatomyositis
Normal value
Dog 2200-6500 U/l
Cat 2000-4000 U/l
Calcium. Ionized calcium.
Calcium is present in blood plasma in three forms:
1) in combination with organic and inorganic acids (a very small percentage),
2) in protein-bound form,
3) in ionized form Ca2+.
Total calcium includes the total concentration of all three forms. Of total calcium, 50% is ionized calcium and 50% is bound to albumin. Physiological changes rapidly alter calcium binding. In a biochemical blood test, both the level of total calcium in the blood serum and separately the concentration of ionized calcium are measured. Ionized calcium is determined in cases where it is necessary to determine the calcium content, regardless of the albumin level.
Ionized calcium Ca2+ is a biologically active fraction. Even a slight increase in plasma Ca2+ can lead to death due to muscle paralysis and coma.
In cells, calcium serves as an intracellular mediator that affects various metabolic processes. Calcium ions take part in the regulation of the most important physiological and biochemical processes: neuromuscular excitation, blood coagulation, secretion processes, maintenance of membrane integrity and transport through membranes, many enzymatic reactions, release of hormones and neurotransmitters, intracellular action of a number of hormones, participates in the process of bone mineralization. Thus, they ensure the functioning of the cardiovascular and neuromuscular systems. The normal course of these processes is ensured by the fact that the concentration of Ca2+ in the blood plasma is maintained within very narrow limits. Therefore, a violation of Ca2+ concentration in the body can cause many pathologies. When calcium levels drop, the most dangerous consequences are ataxia and seizures.
Changes in the concentration of plasma proteins (primarily albumin, although globulins also bind calcium) are accompanied by corresponding changes in the level of total calcium in the blood plasma. The binding of calcium to plasma proteins depends on pH: acidosis promotes the transition of calcium into an ionized form, and alkalosis increases binding to proteins, i.e. reduces the concentration of Ca2+.
Three hormones are involved in calcium homeostasis: parathyroid hormone (PTH), calcitriol (vitamin D), and calcitonin, which act on three organs: bones, kidneys, and intestines. They all work using a feedback mechanism. Calcium metabolism is influenced by estrogens, corticosteroids, growth hormone, glucagon and T4. PTH is the main physiological regulator of calcium concentration in the blood. The main signal influencing the intensity of the secretion of these hormones is the change in ionized Ca in the blood. Calcitonin is secreted by parafollicular c-cells of the thyroid gland in response to an increase in Ca2+ concentration, while it disrupts the release of Ca2+ from the labile calcium store in the bones. When Ca2+ falls, the reverse process occurs. PTH is secreted by the cells of the parathyroid glands and as calcium concentrations fall, PTH secretion increases. PTH stimulates the release of calcium from the bones and the reabsorption of Ca in the renal tubules.
Promotion:
- hyperalbuminemia
- malignant tumors
- primary hyperparathyroidism;
- hypocortisolism;
— osteolytic bone lesions (ostomyelitis, myeloma);
— idiopathic hypercalcemia (cats);
Demotion:
- hypoalbuminemia;
- alkalosis;
- primary hypoparathyroidism;
- chronic or acute renal failure;
- secondary renal hyperparathyroidism;
- pancreatitis;
- unbalanced diet, vitamin D deficiency;
- eclampsia or postpartum paresis;
- impaired absorption from the intestine;
- hypercalcitonism;
- hyperphosphatemia;
- hypomagnesemia;
- enterocolitis;
- blood transfusion;
- idiopathic hypocalcemia;
- extensive soft tissue injury;
Iron
Iron is an important component of heme-containing enzymes and is part of hemoglobin, cytochromes and other biologically important compounds. Iron is a necessary element for the formation of red blood cells and is involved in oxygen transfer and tissue respiration. It also participates in a number of redox reactions, the functioning of the immune system, and collagen synthesis. Developing erythroid cells take up 70 to 95% of the iron circulating in the plasma, and hemoglobin accounts for 55 to 65% of the total iron content in erythrocytes. Iron absorption depends on the age and health of the animal, the state of iron metabolism in the body, as well as the amount of iron and its chemical form. Under the influence of gastric hydrochloric acid, iron oxides ingested in food become soluble and bind in the stomach with mucin and various small molecules that keep iron in a soluble state, suitable for absorption in the alkaline environment of the small intestine. Under normal conditions, only a small percentage of iron from food enters the bloodstream. Iron absorption increases with its deficiency in the body, increased erythropoiesis or hypoxia and decreases with its high total content in the body. More than half of all iron is part of hemoglobin.
It is advisable to test blood for iron on an empty stomach, since there are daily fluctuations in its level with maximum values in the morning. The level of iron in serum depends on a number of factors: absorption in the intestine, accumulation in the liver, spleen, bone marrow, destruction and loss of hemoglobin, synthesis of new hemoglobin.
Increased:
- hemolytic anemia,
- folate deficiency hyperochromic anemia,
- liver diseases,
- administration of corticosteroids
- lead intoxication
Downgraded:
— vitamin B12 deficiency;
- Iron-deficiency anemia;
- hypothyroidism;
- tumors (leukemia, myeloma);
- infectious diseases;
- blood loss;
— chronic liver damage (cirrhosis, hepatitis);
- gastrointestinal diseases.
Chlorine
Chlorine is the main anion of extracellular fluids, present in gastric juice, pancreatic and intestinal secretions, sweat, and cerebrospinal fluid. Chlorine is an important regulator of extracellular fluid volume and plasma osmolarity. Chlorine maintains cell integrity through its effect on osmotic pressure and acid-base balance. In addition, chlorine promotes the retention of bicarbonate in the distal renal tubules.
There are two types of metabolic alkalosis with hyperchloremia:
the chlorine-sensitive type, which can be corrected by the administration of chlorine, occurs with vomiting and the administration of diuretics, as a result of the loss of H+ and Cl- ions;
the chlorine-resistant type, uncorrected by the administration of chlorine, is observed in patients with primary or secondary hyperaldosteronism.
Increased:
- dehydration,
- chronic hyperventilation with respiratory acidosis,
- metabolic acidosis with prolonged diarrhea,
- hyperparathyroidism,
- renal tubular acidosis,
- traumatic brain injury with damage to the hypothalamus,
- eclampsia.
Downgraded:
- general overhydration,
- uncontrollable vomiting or gastric aspiration with alkalosis with hypochloremia and hypokalemia,
- hyperaldosteronism,
- Cushing's syndrome,
— ACTH-producing tumors,
- burns of varying degrees,
- congestive heart failure,
- metabolic alkalosis,
- chronic hypercapnia with respiratory failure,
Normal value:
Dog – 96-122 mmol/l
Cat – 107-129 mmol/l
Potassium
Potassium is the main electrolyte (cation) and a component of the intracellular buffer system. Almost 90% of potassium is concentrated inside the cell, with only small amounts present in the bones and blood. Potassium is concentrated mainly in skeletal muscles, liver and myocardium. Potassium is released from damaged cells into the blood. All potassium that enters the body with food is absorbed in the small intestine. Normally, up to 80% of potassium is excreted in the urine, and the rest in feces. Regardless of the amount of potassium supplied from the outside, it is excreted daily by the kidneys, resulting in rapid hypokalemia.
Potassium is a vital component for the normal formation of membrane electrical phenomena, it plays an important role in the conduction of nerve impulses, muscle contractions, acid-base balance, osmotic pressure, protein anabolism and glycogen formation. Together with calcium and magnesium, K+ regulates heart contraction and cardiac output. Potassium and sodium ions are of great importance in regulating acid-base balance by the kidneys.
Potassium bicarbonate is the main intracellular inorganic buffer. With potassium deficiency, intracellular acidosis develops, in which the respiratory centers react with hyperventilation, which leads to a decrease in pCO2.
Increases and decreases in serum potassium levels are caused by disturbances in the internal and external potassium balance. The external balance factor is: dietary potassium intake, acid-base balance, mineralocorticoid function. Factors of internal balance include the function of adrenal hormones, which stimulate its excretion. Mineralocorticoids directly affect potassium secretion in the distal tubules; glucocorticosteroids act indirectly, increasing glomerular filtration rate and urinary excretion, as well as increasing sodium levels in the distal tubules.
Increased:
- massive muscle injuries
- destruction of the tumor,
- hemolysis, disseminated intravascular coagulation syndrome,
- metabolic acidosis,
- decompensated diabetes mellitus,
- renal failure,
- prescription of anti-inflammatory non-steroidal drugs,
- prescription of K-sparing diuretics,
Downgraded:
- prescription of non-potassium-sparing diuretics.
- diarrhea, vomiting,
- taking laxatives,
- profuse sweating,
- severe burns.
Hypokalemia associated with decreased urinary K+ excretion, but without metabolic acidosis or alkalosis:
- parenteral therapy without additional potassium supplementation,
- starvation, anorexia, malabsorption,
- rapid growth of cell mass when treating anemia with iron, vitamin B12 or folic acid.
Hypokalemia associated with increased K+ excretion and metabolic acidosis:
- renal tubular acidosis (RTA),
- diabetic ketoacidosis.
Hypokalemia associated with increased K+ excretion and normal pH (usually of renal origin):
- recovery after obstructive nephropathy,
- prescription of penicillins, aminoglycosides, cisplatin, mannitol,
- hypomagnesemia,
- monocytic leukemia
Normal values:
Dog – 3.8-5.6 mmol/l
Cat – 3.6-5.5 mmol/l
Sodium
In body fluids, sodium is in an ionized state (Na+). Sodium is present in all fluids of the body, mainly in the extracellular space, where it is the main cation, and potassium is the main cation in the intracellular space. The predominance of sodium over other cations persists in other body fluids, such as gastric juice, pancreatic juice, bile, intestinal juice, sweat, and CSF. Relatively large amounts of sodium are found in cartilage and slightly less in bones. The total amount of sodium in bones increases with age, and the proportion stored decreases. This lobe is clinically important because it represents a reservoir for sodium loss and acidosis.
Sodium is the main component of fluid osmotic pressure. All movements of sodium cause movement of certain amounts of water. The volume of extracellular fluid directly depends on the total amount of sodium in the body. The sodium concentration in plasma is identical to the concentration in the interstitial fluid.
Increased:
- use of diuretics,
- diarrhea (in young animals)
- Cushing's syndrome,
Downgraded:
A decrease in the volume of extracellular fluid is observed when:
- jade with salt loss,
- glucocorticoid deficiency,
- osmotic diuresis (diabetes with glucosuria, condition after a violation of urinary tract obstruction),
- renal tubular acidosis, metabolic alkalosis,
- ketonuria.
A moderate increase in extracellular fluid volume and a normal level of total sodium is observed with:
- hypothyroidism,
- pain, stress
- sometimes in the postoperative period
An increase in the volume of extracellular fluid and an increase in the level of total sodium is observed with:
- congestive heart failure (serum sodium level is a predictor of mortality),
- nephrotic syndrome, renal failure,
- cirrhosis of the liver,
- cachexia,
- hypoproteinemia.
Normal value:
Dog – 140-154 mmol/l
Cat – 144-158 mmol/l
Phosphorus
After calcium, phosphorus is the most abundant mineral element in the body, present in all tissues.
In the cell, phosphorus mainly takes part in the metabolism of carbohydrates and fats or is associated with proteins, and only a small part is in the form of phosphate ion. Phosphorus is part of bones and teeth, is one of the components of nucleic acids, phospholipids of cell membranes, is also involved in maintaining acid-base balance, storing and transferring energy, in enzymatic processes, stimulates muscle contraction and is necessary to maintain neuronal activity. The kidneys are the main regulators of phosphorus homeostasis.
Increased:
— Osteoporosis.
- Use of cytostatics (cytolysis of cells and release of phosphates into the blood).
— Acute and chronic renal failure.
— Bone tissue breakdown (for malignant tumors)
— Hypoparathyroidism,
— Acidosis
— Hypervitaminosis D.
- Portal cirrhosis.
— Healing of bone fractures (formation of bone “callus”).
Downgraded:
- Osteomalacia.
— Malabsorption syndrome.
- Severe diarrhea, vomiting.
— Hyperparathyroidism is the primary and ectopic synthesis of hormones by malignant tumors.
- Hyperinsulinemia (in the treatment of diabetes mellitus).
— Pregnancy (physiological phosphorus deficiency).
— Deficiency of somatotropic hormone (growth hormone).
Normal value:
Dog – 1.1-2.0 mmol/l
Cat – 1.1-2.3 mmol/l
Magnesium
Magnesium is an element that, although found in small quantities in the body, is of great importance. About 70% of the total amount of magnesium is found in bones, and the rest is distributed in soft tissues (especially skeletal muscles) and in various fluids. Approximately 1% is found in plasma, 25% is bound to proteins, and the remainder remains in ionized form. Most magnesium is found in the mitochondria and nucleus. In addition to its plastic role as a constituent of bones and soft tissues, Mg has many functions. Together with sodium, potassium and calcium ions, magnesium regulates neuromuscular excitability and the blood clotting mechanism. The actions of calcium and magnesium are closely related, and a deficiency of one of the two elements significantly affects the metabolism of the other (magnesium is necessary for both intestinal absorption and calcium metabolism). In muscle cells, magnesium acts as a calcium antagonist.
Magnesium deficiency leads to calcium mobilization from bones, so it is recommended to consider calcium levels when assessing magnesium levels. From a clinical point of view, magnesium deficiency causes neuromuscular diseases (muscle weakness, tremors, tetany and convulsions), and can cause cardiac arrhythmias.
Increased:
- iatrogenic causes
- kidney failure
- dehydration;
- diabetic coma
- hypothyroidism;
Downgraded:
— diseases of the digestive system: malabsorption or excessive loss of fluids through the gastrointestinal tract;
- renal diseases: chronic glomerulonephritis, chronic pyelonephritis, renal tubular acidosis, diuretic phase of acute tubular necrosis,
- use of diuretics, antibiotics (aminoglycosides), cardiac glycosides, cisplatin, cyclosporine;
- endocrine disorders: hyperthyroidism, hyperparathyroidism and other causes of hypercalcemia, hyperparathyroidism, diabetes mellitus, hyperaldosteronism,
- metabolic disorders: excessive lactation, last trimester of pregnancy, insulin treatment of diabetic coma;
- eclampsia,
- osteolytic bone tumors,
- progressive Paget's disease of bones,
- acute and chronic pancreatitis,
- severe burns,
- septic conditions,
- hypothermia.
Normal value:
Dog – 0.8-1.4 mmol/l
Cat – 0.9-1.6 mmol/l
Bile acids
Determination of total bile acids (BA) in the circulating blood is a liver function test due to a special process of bile acid recycling called enterohepatic circulation. The main components involved in the recycling of bile acids are the hepatobiliary system, the terminal ileum and the portal vein system.
Circulation disorders in the portal vein system in most animals are associated with portosystemic shunting. Portsystemic shunt is an anastomosis between the veins of the gastrointestinal tract and the caudal vena cava, due to which the blood flowing from the intestines does not undergo purification in the liver, but immediately enters the body. As a result, compounds that are toxic to the body, primarily ammonia, enter the bloodstream, causing severe disorders of the nervous system.
In dogs and cats, most of the bile produced is usually stored in the gallbladder before meals. Eating stimulates the release of cholecystokinin from the intestinal wall, which causes contraction of the gallbladder. There is individual physiological variability in the amount of bile stored and the degree of gallbladder contraction during food stimulation, and the relationship between these values changes in some sick animals.
When circulating bile acid concentrations are within or close to the standard range, such physiological fluctuations can cause postprandial bile acid levels to be similar to or even lower than fasting levels. In dogs, this can also occur when there is an overgrowth of bacteria in the small intestine.
Increased levels of bile acids in the blood, secondary to liver disease or portosystemic shunting, are accompanied by increased excretion in the urine. In dogs and cats, determination of the bile acids/creatinine ratio in urine is a fairly sensitive test for diagnosing liver diseases.
It is important to study the level of bile acids on an empty stomach and 2 hours after meals.
Rarely, there may be false negative results resulting from severe intestinal malabsorption.
Increased:
— hepatobiliary diseases, in which there is a violation of the secretion of fatty acids through the biliary tract (obstruction of the intestines and bile ducts, cholestasis, neoplasia, etc.);
- circulatory disorders in the portal vein system,
— portsystemic shunt (congenital or acquired);
— terminal stage of liver cirrhosis;
- microvascular dysplasia of the liver;
- impairment of the ability of hepatocytes to absorb fatty acids, characteristic of many liver diseases.
Normal value:
Dog 0-5 µmol/l
A urine test is important for a person who can tell the doctor where and how it hurts, and even more so for a dog, which, unfortunately, cannot tell us about its pain.
However, if taking a urine test to a medical laboratory is normal, going to a veterinary laboratory with dog excrement is still quite rare.
Factors influencing the composition of urine in dogs
Urine that is excreted (diuresis) is a waste product of the body. Its composition is influenced by:
- pathological factors (infection, invasion,);
- physiological (pregnancy, estrus, weight, type of feeding);
- climatic (temperature, humidity).
Stress can affect the composition of your urine.
Conducting experiments and studies with clinically healthy animals, biologists calculated the parameters that are present in urine and characterize the physiological balance of the functioning of systems and organs.
Composition and parameters of the norm
The basis of urine is water, its normal content is 97–98%. The following components are included in its composition:
- organic;
- inorganic.
According to physical parameters, a dog’s urine should be yellow or light yellow (depending on the food consumed), transparent, and without a strong odor.
Normally, the color of urine should be yellow.
Table of organic components (norm for dogs)
Density
The specific gravity of urine is an indicator that characterizes how much the kidneys can concentrate urine by reabsorbing water.
The density of urine allows you to assess kidney activity.
pH Indicator of acid balance
Urine, normally, can be either acidic or alkaline. By this indicator we can judge the dog’s feeding diet. The more protein food is contained in the four-legged bowl, the more acidic the urine.
Protein feeds increase the acidity of urine.
The indicator will be acidified during fasting or prolonged physical activity, but this will not indicate pathology.
Protein
A substance consisting of amino acids should not normally leave the body.
The appearance of protein in the urine may sometimes not be associated with pathology. This phenomenon occurs with excessive physical exertion, as well as overfeeding the dog with food of animal origin, or when the diet is not balanced in protein.
The appearance of protein occurs during heavy physical activity.
Glucose
An indicator that makes it possible to understand whether carbohydrate metabolism is occurring correctly in a dog.
Normally, all carbohydrates should be absorbed, but if there is an excess of them in the diet, then some of them will be excreted in the urine.
Excess glucose will be excreted in the urine.
Often this message is deceptive. Since diagnostic strips react to the level of ascorbic acid, and a dog can synthesize it in fairly high concentrations.
Bilirubin
A component of bile. The appearance of traces of bilirubin may indicate.
Detected bilirubin indicates liver pathologies.
Ketone bodies
If ketone bodies are found along with increased sugar content, this indicates.
Ketone bodies alone can be normal during prolonged fasting, or when there is an excess of fat in the dog’s diet.
Ketone bodies are released during fasting.
Microscopic studies
After settling, the urine releases sediment. Having examined it under a microscope, its components are divided into organic and mineral origin.
Under a microscope, the urine sediment is divided into parts.
Organic sediments
- Red blood cells can be found as organic. Such a “find” may indicate a pathology of the urinary tract.
- Leukocytes can be found normally, but not more than 1–2. If the quantity is higher, this indicates kidney pathology.
- Epithelial cells are always present in urine sediment, since the epithelial cover is constantly changing, but this indicator is more pronounced in females.
- If detected increased number of cylinders , then this may indicate pathology of the kidneys and urinary system.
The presence of red blood cells indicates urinary tract disease.
Inorganic sediments
If the urine pH is acidic, then uric acid, calcium phosphate, and calcium sulfate may predominate. If the reaction is closer to alkaline, then amorphous phosphates, magnesium phosphate, calcium carbonate, tripel phosphate may be present.
When uric acid appears (normally it should not be present), we can talk about strong physical exertion on the dog, or overfeeding with meat food. In pathological processes such as uric acid diathesis, feverish conditions, tumor processes, uric acid will be present in significant quantities.
When you overfeed meat, uric acid appears.
If the dog's urine is closer to brick in color, then amorphous urates will precipitate. Under physiological conditions, such processes are impossible. The presence may indicate fever.
Oxalates
Oxalates (producers of oxalic acid) can be in units. If there are many of them in the field of view, then diabetes mellitus, pyelonephritis, and calcium pathology are possible.
The detection of calcium carbonate will not be a pathology if the dog is fed exclusively with food of plant origin, otherwise it will indicate.
If your dog is a Dalmatian Great Dane or a puppy, ammonium urate will be present in the urine normally. In other cases, it may indicate bladder inflammation.
In Dalmatian Great Danes, the presence of ammonium urate is normal.
Crystals and neoplasms
- If found tyrosine or leucine crystals , then the pathology can be caused by leukemia or phosphorus poisoning.
- On kidney tumors , or degenerative processes in them will be indicated by the presence of cholesterol crystals in the sediment.
Tyrosine crystals can be caused by leukemia.
Fatty acid
Sometimes fatty acids can be detected in the urine. Their presence indicates dystrophic changes in the renal tissue, namely the disintegration of the epithelium of the renal tubules.
The presence of fatty acids indicates changes in the kidney tissue.
Bacteriological urine analysis
The detection of bacteria in the field of view of a microscope cannot indicate pathology or normality, but the fact itself is a prerequisite for conducting bacterial analysis.
When inoculating urine on nutrient media and identifying the level ranging from 1000 to 10000 microbial bodies in one milliliter of urine, for females this will be the norm, but for males, it may indicate the onset of inflammatory processes in the genitourinary organs.
Such a urine test is carried out, as a rule, not so much to identify microflora, but to isolate a pure culture and subtitrate the sensitivity of antibiotics, which are then used to treat the animal.
Bacteriological analysis of urine is carried out to determine sensitivity to antibiotics.
Urine analysis for fungi
When sown on nutrient media, microscopic fungi germinate at certain temperatures. Normally, they are absent, but long-term treatment with antibiotics, as well as diabetes mellitus, can activate the growth of pathogenic microflora.
Urinalysis can be carried out qualitatively, using test systems (strips that are not always adapted for veterinary diagnostics) and quantitatively, in the laboratory.
If the initial analysis of the test system showed deviations in one direction or another, this is not yet a reason to panic. Quantitative measurements of urine parameters are necessary. Research should be carried out in a veterinary laboratory, and only one that has the right to conduct certain research.
Urinalysis must be performed in a laboratory setting.
conclusions
It is necessary to clearly understand that not having research results is better than having incorrect ones. Urine examination is intended not only to identify pathology, but also to differentiate the disease. Any inaccuracy can lead to the prescription of incorrect treatment, which in turn can lead to irreversible consequences.
Urine examination will help to identify pathologies in time.
Video about dog urine analysis
Urolithiasis (urolithiasis) in dogs is a phenomenon of the formation and presence of uroliths in the urinary tract (kidneys, ureters, bladder and urethra). Uroliths ( uro– urine, lith– stone) - organized concretions consisting of minerals (primarily) and a small amount of organic matrix.
There are three main theories of the formation of urinary stones: 1. Precipitation-crystallization theory; 2. Matrix-nucleation theory; 3. Crystallization–inhibition theory. According to the first theory, oversaturation of urine with one or another type of crystals is put forward as the main reason for the formation of stones and, consequently, urolithiasis. In the theory of matrix nucleation, the presence of various substances in the urine that initiate the onset of urolith growth is considered as the reason for the formation of uroliths. In the theory of crystallization-inhibition, it is assumed that there are factors in the urine that inhibit or provoke the formation of stones. Oversaturation of urine with salts in dogs is considered to be the main cause of urolithiasis; other factors play a less significant role, but can also contribute to the pathogenesis of stone formation.
Most canine uroliths are identified in the bladder or urethra. The predominant type of urinary stones are struvite and oxalate, followed by urate, silicate, cystine and mixed types in frequency of occurrence. The last twenty years have seen an increased percentage of oxalates, presumably this phenomenon developed due to the widespread use of industrial feed. An important cause of struvite formation in dogs is urinary tract infection. Below are the main factors that can increase the risk of dogs developing one or another type of urolithiasis.
Risk factors for the development of urolithiasis in dogs with the formation of oxalates
Oxalate urinary stones are the most common type of uroliths in dogs; the incidence of urolithiasis with this type of stones has increased significantly over the past twenty years, along with a decrease in the incidence of struvite-predominant stones. Calcium oxalate urinary stones contain calcium oxalate monohydrate or dihydrate, and the outer surface usually has sharp, jagged edges. From one to many uroliths can form, the formation of oxalates is characteristic of acidic dog urine.
Possible reasons for the increased incidence of oxalate uroliths in dogs include demographic and dietary changes in dogs that have occurred during this period. These factors may include feeding an acidifying diet (widespread use of industrial feeds), an increase in the incidence of obesity and an increase in the percentage of breeds prone to the formation of a certain type of stone.
A breed predisposition to urolithiasis with the formation of oxalates has been noted in representatives of such breeds as the Yorkshire Terrier, Shih Tzu, Miniature Poodle, Bichon Frize, Miniature Schnauzer, Pomeranian, Cairn Terrier, Maltese and Kesshund. Gender predisposition has also been noted in castrated males of small breeds. Urolithiasis due to the formation of oxalate stones is more often observed in middle-aged and elderly animals (average age 8-9 years).
In general, the formation of uroliths is more related to the acid-base balance of the animal's body than to the specific pH and composition of urine. Dogs with oxalate urolithiasis often exhibit transient hypercalcemia and hypercalciuria after feeding. Thus, uroliths can form against the background of hypercalcemia and the use of calciuretics (eg furosemide, prednisolone). Unlike struvite, urinary tract infection with oxalate uroliths develops as a complication of urolithiasis, and not as the root cause. Also, with the oxalate form of urolithiasis in dogs, there is a high percentage of relapse after stone removal (about 25%-48%).
Risk factors for the development of urolithiasis in dogs with struvite formation
According to some data, the percentage of struvite urolithiasis to the total number is 40%-50%, but in recent years there has been a significant decrease in the incidence of struvite urolithiasis in favor of oxalate urolithiasis (see above). Struvite consists of ammonium, magnesium and phosphate ions, the shape is rounded (spherical, ellipsoidal and tetrahedral), the surface is often smooth. With struvite urolithiasis, both single and multiple uroliths with different diameters can form. Struvite in the canine urinary tract is most often located in the bladder, but can also occur in the kidneys and ureter.
The vast majority of canine struvite urinary stones are induced by a urinary tract infection (usually Staphylococcus intermedius, but may also play a role Proteus mirabilis.). Bacteria have the ability to hydrolyze urea to ammonia and carbon dioxide, this is accompanied by an increase in urine pH and contributes to the formation of struvite urinary stones. In rare cases, dog urine can be oversaturated with the minerals that make up struvite, and then urolithiasis develops without the involvement of infection. Based on the possible causes of struvite urolithiasis in dogs, even with a negative urine culture, the search for infection continues and it is preferable to culture the bladder wall and/or stone.
With urolithiasis in dogs with the formation of struvite uroliths, a breed predisposition has been noted in such representatives as the miniature schnauzer, bichon frise, cocker spaniel, shitzu, miniature poodle and Lhasa apso. Age predisposition was noted in middle-aged animals, and gender predisposition in females (presumably due to an increased incidence of urinary tract infections). The American Cocker Spaniel may have a predisposition to form sterile struvites.
Risk factors for the development of urolithiasis in dogs with the formation of urates
Urate urinary stones account for about a quarter (25%) of all stones delivered to specialized veterinary laboratories. Urate stones consist of a monobasic ammonium salt of uric acid, are small in size, their shape is spherical, the surface is smooth, the multiplicity of urolithiasis is characteristic, the color ranges from light yellow to brown (maybe green). Urate stones usually crumble easily, and concentric layering is visible on the fracture. With urate urolithiasis, a certain predisposition to urolithiasis has been noted in male dogs, presumably due to the smaller lumen of the urethra. Also, with urolithiasis in dogs with the formation of urates, a high percentage of relapses after stone removal is characteristic, it can be 30%-50%.
Unlike representatives of other breeds, the Dalmatian has a violation of purine metabolism, which leads to the release of increased amounts of uric acid and a predisposition to the formation of urates. It should be remembered that not all Dalmatians develop urates, despite the congenital elevated level of uric acid in the animal’s urine; a clinically significant disease is detected in animals in 26%-34% of cases. Some other breeds (English Bulldog and Black Russian Terrier) may also have a hereditary predisposition to impaired purine metabolism (similar to Dalmatians) and a tendency to the urate form of urolithiasis.
Another reason for the formation of urates is microvascular dysplasia of the liver, which disrupts the conversion of ammonia to urea and uric acid to allantoin. With the above disorders of the liver, a mixed form of urolithiasis is more often observed; in addition to urates, struvite is also formed. A breed predisposition to the formation of this type of urolithiasis has been noted in breeds predisposed to the formation (eg Yorkshire Terrier, Miniature Schnauzer, Pekingese).
Risk factors for the development of urolithiasis in dogs with the formation of silicate stones
Silicate uroliths are also rare and cause urolithiasis in dogs (about 6.6% of the total number of urinary stones), they consist mostly of silicon dioxide (quartz), and may contain small amounts of other minerals. The color of silicate urinary stones in dogs is gray-white or brownish, and multiple uroliths are more often formed. A predisposition to the formation of silicate stones has been noted in dogs fed a diet high in gluten grains (gluten) or soybean skins. The relapse rate after stone removal is quite low. As with oxalate urolithiasis, urinary tract infection is considered a complicating rather than a causative factor in the disease.
Risk factors for the development of urolithiasis in dogs with the formation of cystine
Cystine uroliths are rare in dogs (about 1.3% of the total number of urinary stones), they consist entirely of cystine, they are small in size, spherical in shape. The color of cystine stones is light yellow, brown or green. The presence of cystine in the urine (cystinuria) is considered a hereditary pathology with impaired transport of cystine in the kidneys (± amino acids), the presence of cystine crystals in the urine is regarded as a pathology, but not all dogs with cystinuria form the corresponding urinary stones.
A number of dog breeds have been shown to have a breed predisposition to the disease, such as the English Mastiff, Newfoundland, English Bulldog, Dachshund, Tibetan Spaniel and Basset Hound. Cystine urolithiasis in dogs has an exclusive gender predisposition in males, with the exception of the Newfoundland. The average age of onset of the disease is 4-6 years. When removing stones, a very high percentage of relapses of their formation was noted, it is about 47%–75%. As with oxalate urolithiasis, urinary tract infection is considered a complicating rather than a causative factor in the disease.
Risk factors for the development of urolithiasis in dogs with the formation of hydroxyapatite (calcium phosphate)
This type of urolith is extremely rarely observed in dogs, and apatite (calcium phosphate or calcium hydroxyl phosphate) often acts as a component of other urinary stones (usually struvite). Alkaline urine and hyperparathyroidism predispose to precipitation of hypoxyapatitis in the urine. The following breeds have been shown to be predisposed to the formation of this type of urinary stones: Miniature Schnauzer, Bichon Frize, Shih Tzu and Yorkshire Terrier.
Clinical signs
Struvite urinary stones are more often found in females, due to their increased susceptibility to urinary tract infections, however; clinically significant urethral obstruction is more common in male dogs due to the narrower and longer urethra. Urolithiasis in dogs can occur at any age, but is more common in middle-aged and elderly animals. Urinary stones in dogs under 1 year of age are most often struvite and develop due to a urinary tract infection. With the development of the oxalate form of urolithiasis in dogs, the development of stones is more often observed in males, especially in breeds such as miniature schnauzer, Shitzu, Pomeranian, Yorkshire terrier and Maltese. Also, oxalate urolithiasis in dogs is observed at an older age compared to the struvite type of urolithiasis. Urates are more often formed in Dalmatians and English bulldogs, as well as dogs predisposed to the development. Cystine uroliths also have a certain breed predisposition; the table below contains general information on the incidence of urolithiasis in dogs.
Table. Breed, gender and age predisposition for the formation of urinary stones in dogs.
|
Type of stones |
Morbidity |
|
Struvite |
Breed Predisposition: Miniature Schnatsuer, Bichon Frize, Cocker Spaniel, Shih Tzu, Miniature Poodle, Lhasa Apso. Sexual predisposition in females Age predisposition – middle age The main predisposing factor to the development of struvitis is infection of the urinary tract with urease-producing bacteria (ex. Proteus, Staphylococcus). |
|
Oxalates |
Breed Predisposition – Miniature Schnauzer, Shih Tzu, Pomeranian, Yorkshire Terrier, Maltese, Lhasa Apso, Bichon Frize, Cairn Terrier, Miniature Poodle Sexual predisposition – more often in castrated males than in non-castrated males. Age predisposition: middle and old age. One of the predisposing factors is obesity |
|
Breed predisposition – Dalmatian and English bulldog The main factor predisposing to the development of urates is a portosystemic shunt, and accordingly it is more often observed in predisposed breeds (eg Yorkshire Terrier, Miniature Schnauzer, Pekingese) |
|
|
Silicates |
Breed predisposition – German Shepherd, Old English Sheepdog Gender and age predisposition – middle-aged males |
|
Breed Predisposition – Dachshund, Basset Hound, English Bulldog, Newfoundland, Chihuahua, Miniature Pinscher, Welsh Corgi, Mastiffs, Australian Cowdog Gender and age predisposition – middle-aged males |
|
|
Calcium phosphate |
Breed predisposition – Yorkshire Terrier |
The history of urolithiasis in dogs depends on the specific location of the stone, the duration of its presence, various complications and diseases predisposing to the development of the stone (etc.).
When urinary stones are found in the kidneys, animals are characterized by a long asymptomatic course of urolithiasis; there may be blood in the urine (hematuria) and signs of pain in the kidney area. With the development of pyelonephritis, the animal may experience fever, polydipsia/polyuria and general depression. Ureteral stones are rarely diagnosed in dogs, dogs may present with various signs of lumbar pain, most animals are more likely to develop a unilateral lesion without systemic involvement, and the stone may be discovered as an incidental finding in the setting of renal hydronephrosis.
Canine bladder stones represent the vast majority of cases of canine urolithiasis; the owner's complaint upon presentation may include signs of difficulty and frequent urination, and sometimes hematuria. The displacement of stones into the urethra of male dogs can lead to partial or complete obstruction of the outflow of urine, in which case the primary complaints may be signs of strangury, abdominal pain and signs of postrenal renal failure (eg anorexia, vomiting, depression). In rare cases of complete obstruction of urine outflow, complete rupture of the bladder with signs of uroabdomen may develop. It should be remembered that urinary tract stones in dogs can be asymptomatic and are detected as an incidental finding during plain radiographic examination.
Physical examination data for urolithiasis suffer from poor specificity of symptoms. With unilateral hydronephrosis in dogs, an enlarged kidney (renomegaly) may be detected during palpation examination. With obstruction of the ureters or urethra, pain in the abdominal cavity can be determined; with rupture of the urinary tract, signs of the uroabdomen and general depression develop. During a physical examination, bladder stones can be detected only if they are of a significant number or volume; upon palpation, the sounds of crepitus can be detected or a urolith of significant size can be palpated. With obstruction of the urethra, palpation of the abdomen can reveal an enlarged bladder, rectal palpation can reveal a stone localized in the pelvic urethra, and if the stone is localized in the urethra of the penis, in some cases it can be palpated. When attempting to catheterize the bladder of an animal with urethral obstruction, a veterinary clinician may identify mechanical resistance to the catheter.
The most radiopaque urinary stones are uroliths containing calcium (calcium oxalates and phosphates); struvites are also well identified by plain radiographic examination. The size and number of radiopaque stones is best determined by X-ray examination. Double contrast cystography and/or retrograde urethrography can be used to identify radiolucent stones. Ultrasound diagnostic methods can detect radiolucent stones in the ureter of the bladder and urethra, in addition, ultrasound can help in assessing the kidneys and ureter of the animal. When examining a dog with urolithiasis, radiographic and ultrasound methods are usually used together, but, according to many authors, double contrast cystography is the most sensitive method for identifying bladder stones.
Laboratory tests for a dog with urolithiasis include a complete blood count, a biochemical profile of the animal, a complete urinalysis, and a urine culture. With canine urolithiasis, even in the absence of obvious urinary tract infection, hematuria and proteinuria, there is still a high probability of urinary tract infection, and it is preferable to use additional research methods (eg urine cytology, urine culture). A biochemical blood test can detect signs of liver failure (eg high blood urea nitrogen levels, hypoalbuminemia) in dogs with.
Diagnosis and differential diagnosis
Urinary stones should be suspected in all dogs with signs of urinary tract infection (eg hematuria, stranguria, pollakiuria, urinary obstruction). The list of differential diagnoses includes any form of bladder inflammation, urinary tract neoplasms, and granulomatous inflammation. Detection of uroliths as such is carried out through visual examination methods (radiography, ultrasound), in rare cases, identification of uroliths is possible only intraoperatively. Determining the specific type of urolith requires its examination in a specialized veterinary laboratory.
It should be remembered that the identification of most crystals in urine does not always indicate pathology (with the exception of cystine crystals); in many dogs with urolithiasis, the type of crystals found in the urine may differ in composition from urinary stones; crystals may not be detected at all, or multiple crystals may be detected without the risk of urinary stone formation.
Treatment
The presence of urinary stones in the urinary tract of dogs is not always associated with the development of clinical signs; in many cases, the presence of uroliths is not accompanied by any symptoms on the part of the animal. In the presence of uroliths, several scenarios may occur: their asymptomatic presence; evacuation of small uroliths into the spring environment through the urethra; spontaneous dissolution of urinary stones; growth cessation or continuation; addition of a secondary urinary tract infection (); partial or complete obstruction of the ureter or urethra (if the ureter is blocked, unilateral hydronephrosis may develop); formation of polypoid inflammation of the bladder. The approach to a dog with urolithiasis largely depends on the manifestation of certain clinical signs.
Urethral obstruction is an emergency, and if it develops, a number of conservative measures can be taken to displace the stone either outward or back into the bladder. In females, rectal palpation with massage of the urethra and urolith towards the vagina can promote its exit from the urinary tract. In both females and males, the urethrohydropuslation method can push the urinary stone back into the bladder and restore normal urine flow. In some cases, when the diameter of the urolith is smaller than the diameter of the urethra, descending urohydropulsion can be used, when a sterile saline solution is injected into the bladder of an animal under anesthesia, followed by manual emptying in an attempt to remove stones (the procedure can be performed several times).
Once the stone has been displaced into the bladder, it can be removed by cytostomy, endoscopic laser lithotripsy, endoscopic basket extraction, laparoscopic cystotomy, dissolved by drug therapy, or destroyed by extracorporeal shock wave lithotripsy. The choice of method depends on the size of the animal, the necessary equipment and the qualifications of the veterinarian. If it is impossible to move the stone from the urethra, urethrotomy can be used in male dogs, followed by removal of the stone.
Indications for surgical treatment of urolithiasis in dogs include such indicators as obstruction of the urethra and ureter; multiple recurrent episodes of urolithiasis; lack of effect from attempts to conservatively dissolve stones within 4-6 weeks, as well as the personal preferences of the doctor. When localizing uroliths in the kidneys of dogs, pyelotomy or nephrotomy can be used; it should be remembered that in dogs, uroliths of the kidneys and bladder can also be crushed using extracorporeal shock wave lithotripsy. If urinary stones are found in the ureters and localized in the proximal areas, ureteretomy can be used; if they are localized in the distal parts, resection of the ureter can be used, followed by the creation of a new connection with the bladder (ureteroneocystostomy).
Indications for conservative treatment of urolithiasis in dogs are the presence of soluble uroliths (struvite, urate, cystine and maybe xanthine) as well as animals with concomitant diseases that increase the surgical risk. Regardless of the composition of the urolith, general measures are taken in the form of increased water consumption (and therefore increased diuresis), treatment of any underlying diseases (eg Cushing's disease) as well as bacterial therapy (primary or secondary). It should be remembered that bacterial infection (cystitis or pyelonephritis) makes a significant contribution to the development of urolithiasis in dogs, either as a trigger or as a maintaining mechanism. The effectiveness of conservative dissolution of canine urinary stones is usually monitored by visual examination (usually x-ray).
With struvite urolithiasis, the main reason for their formation in dogs is a urinary tract infection, and they dissolve with adequate antibacterial therapy, possibly with the combined use of dietary feeding. At the same time, the average time for dissolution of infected uroliths in dogs during treatment is about 12 weeks. With the sterile form of struvite urolithiasis in dogs, the time required for the dissolution of urinary stones is much shorter and takes about 4-6 weeks. In dogs with struvite urolithiasis, a change in diet may not be necessary to dissolve stones; reverse development of stones is observed only against the background of appropriate antibacterial therapy and increased water consumption.
In dogs with urate form of urolithiasis, in an attempt to conservatively dissolve stones, allopurinol can be used at a dose of 10-15 mg/kg PO x 2 times a day, as well as alkalinization of urine by changing the diet. The effectiveness of conservative dissolution of urates is less than 50% and takes an average of 4 weeks. It should be remembered that a significant cause of the formation of urates in dogs is, and the dissolution of stones can be observed only after surgical resolution of this problem.
For cystine uroliths in dogs, in an attempt to conservatively treat urolithiasis, 2-mercatopropionol glysine (2-MPG) 15-20 mg/kg PO x 2 times a day can be used, as well as feeding an alkalizing diet low in protein. The dissolution time for cystine stones in dogs takes about 4-12 weeks.
Xanthine uroliths are treated by reducing the dose of allopurinol and a low-purine diet; there is a possibility of their reverse development. With oxalate uroliths, there are no proven methods for their dissolution and it is generally accepted that they cannot be reversed despite all the measures taken.
Valery Shubin, veterinarian, Balakovo
Loading...