April 2009

Urology

Jody P. Lulich, DVM, PhD, DACVIM
University of Minnesota




Urinalysis: Performing an Accurate Urine Sediment Analysis

URINE COLLECTION

I. HOW SHOULD URINE BE COLLECTED FOR ANALYSIS?


The urine collection method may vary depending on the tests selected, disease location, patient cooperation, and veterinarian experience (Table 1). However, cystocentesis has become the standard of practice for most clinical situations (Table 2). It is easy to perform and well tolerated by patients. In addition, urine samples collected by cystocentesis are devoid of contaminants from the distal urogenital tract, thereby strengthening the validity of results.

What You Will Need?
  • 22 gauge needles; 1.5-inch hypodermic or 3-inch spinal needle may be selected depending on size of patient and distance of ventral bladder wall from ventral abdominal wall
  • 3- to 12-ml syringes. Most normal reference values for urine sediment are based on centrifugation of 5-ml urine, so we generally use 6-ml syringes
  • Cotton balls or gauze saturated with 70% alcohol or 70% alcohol in a spray bottle.
Table 1. PREFERRED METHOD OF URINE COLLECTION ON THE BASIS OF PATIENT SAFETY AND DIAGNOSTIC
QUALITY OF SAMPLE FOR COMMON CLINICAL PRESENTATIONS



Clinical Presentation
Collection Method
Cystocentesis Voided
Initial Stream
Voided
Midstream
Catheterization Manual expression
Screening Urinalysis P I A I I
Diagnostic urine culture P I A I I
Therapeutic urine culture P I I I I
IFLUTD P I A II
Urolithiasis P A A II
Urethral disease A P A II
Prostatic disease A P A II
Monitoring Hematuria I P P II
Bladder neoplasia I P P II
Ascities I I P II

P = preferable, A = acceptable, I = inadvisable


Table 2. DIAGNOSTIC CYSTOCENTESIS: ADVANTAGES AND DISADVANTAGES


ADVANTAGES
  1. Quick and easy to perform
  2. Less risk of iatrogenic urinary tract infection than with transurethral catheterization
  3. Prevents contamination of urine samples that frequently occurs when voided through the urethra and genital tract.
  4. Aids in localization of hematuria, pyuria and bacteriuria
DISADVANTAGES
  1. Dependent on an adequate volume of urine to allow palpation and immobilization of the urinary bladder
  2. Frequently associated with needle induced microscopic hematuria
  3. May be associated with implantation of neoplastic bladder cells along the pathway of the needle.
  4. The chance of contaminating the urine sample with abdominal or intestinal contents is greatest when cystocentesis is preformed blindly
Patient Considerations

To minimize iatrogenic trauma to the urinary bladder and adjacent structures and contaminating the urine sample with blood, routine cystocentesis should not be performed unless a sufficient amount of urine in is the lumen to permit localization and immobilization of the bladder by abdominal palpation. Blind cystocentesis without digital localization and immobilization (or localization with ultrasonography) of the urinary bladder is usually unsuccessful and increases iatrogenic risk. To reduce the likelihood of the patient voiding before urine collection, we advise owners to avoid situations that trigger urination in their pets. For example, small dogs can be carried from their car to the hospital and held until cystocentesis can be performed. Cats may be placed in a kennel without a litter pan several hours before urine collection.

Because insertion of a 22-gauge needle through the walls of the abdomen and urinary bladder is associated with little discomfort, tranquilization or anesthesia is rarely required. If needed, uncooperative patients resisting abdominal palpation or mild physical restraint may be more easily handled using distractive maneuvers or chemical sedation. Placing blankets or foam pads between the patient and the examination table may improve patient comfort and cooperation when they are restrained in dorsal or lateral recumbency.

Depending on severity of dysuria, cystocentesis may not be feasible in cats with idiopathic lower urinary tract disease. To facilitate urine collection, administer analgesia (e.g., buprenorphine 0.03mg/kg, IV, IM, sublingual q8hr) 12 to 24 hours before cystocentesis. If cystocentesis is still not possible, a voided sample may have to suffice.

It may be difficult to palpate the urinary bladder of an obese patient. In this situation, ultrasonography may be used to guide the needle.

If the urinary bladder does not contain sufficient urine, the patient may be given fluids or a diuretic. Although diuretics, such as furosemide (0.25 to 0.5 mg/kg IV or SC), may be used to rapidly increase urine production, alterations of urine specific gravity, pH, and other components of the urinalysis are notable drawbacks of these agents. Even the quantity of bacteria per milliliter of urine may be substantially reduced, altering results of quantitative urine culture. Diuretics to enhance urine collection by augmenting urine flow are thus best suited for serial urine sample collection when information about urine specific gravity and semiquantitative evaluation of routine test components are not significant.

Site Considerations


Careful planning minimizes risk. We recommend insertion of the needle into the ventral or ventrolateral wall of the urinary bladder to minimize the chance of trauma to the ureters and major abdominal blood vessels (Figure 1). Direct the needle caudally, penetrating the bladder wall at an oblique angle (about 45 degrees), with the tip of the needle terminating at a safe distance from the bladder's attachment to the urethra rather than the vertex. This permits removal of urine without the need to reinsert the needle if the bladder contracts substantially.
One study reported that clipping the hair and disinfecting the skin had no effect on results of urine samples submitted for urinalysis and bacterial culture compared with samples collected without these procedures.1 However, this study was not designed to assess the effects of lack of disinfection on the patient. To facilitate palpation and visualization of the bladder, minimize iatrogenic infection to the patient, and accurately insert the needle through the abdominal skin (and not your hand); clip excessive fur (the ventral midline is relatively hairless; therefore clipping may not be necessary) and swab the fur and skin with alcohol.

How to Perform Diagnostic Cystocentesis
  1. To minimize trauma from needle movement, hold the syringe (with attached needle) with your thumb and first two fingers (Figure 2). This grasp allows you to insert the needle into the bladder and aspirate urine into the syringe (by withdrawing the plunger of the syringe with your second finger [arrow]) without repositioning the syringe in your hand.

  2. The patient may be placed in dorsal, right lateral, or left lateral recumbency or in a standing position. If you are right-handed, hold the syringe in your right hand and have the patient's head to your right side (or vice versa if you are left-handed). This facilitates needle advancement in a caudal direction and allows the needle tip to remain in the bladder lumen (i.e., as urine is removed, the vertex of the bladder contracts caudally toward its junction with the urethra).

  3. Success is dependent on palpation and immobilization of the urinary bladder. Palpate slowly to allow the patient to become accustomed to your touch. If you are right-handed, localize and stabilize the bladder with your left hand (or vice versa if you are left-handed). Because the bladder is secured caudally by its attachment to the urethra, grasping the caudal aspect of the bladder and applying traction in a cranial direction helps stabilize it during the procedure. When cystocentesis is performed in a patient positioned in lateral recumbency, support the back to minimize movement during palpation. In this position, the needle can be directed dorsocaudally or laterocaudally. Be careful not to apply excessive digital pressure to the bladder wall.

  4. Insert the needle through the ventral abdominal wall, advancing it toward the caudoventral aspect of the bladder. When performing cystocentesis in a dog in a standing position, lift the skin and hair of the flank dorsally to facilitate visualization of the site of needle insertion. If the dog is in dorsal recumbency, insert the needle in front of or lateral to the prepuce, depending on the size and position of the urinary bladder.
    Precise location of entry of the needle into the bladder wall is not critical. The needle should be inserted at an oblique angle (about 45 degrees). With this approach, elasticity of bladder musculature and the interlacing arrangement of individual muscle fibers provides a better seal of the pathway created by the needle when it is removed. In addition, subsequent distention of the bladder wall as the lumen refills with urine tends to force the walls of the needle tract into apposition.

  5. To enhance recovery of crystalline material that may have gravitated to the dependent portion of the bladder lumen, gently agitate the urine within the bladder via abdominal palpation just before inserting the needle into the abdominal wall. If urine cannot be aspirated, withdraw the needle and discard it along with the syringe because it may contain blood that will contaminate the urine sample. In addition, a new needle and syringe minimize iatrogenic microbial infection from the intestine and skin. If several attempts are unsuccessful, wait until sufficient urine has accumulated in the bladder.
    Ultrasound-guided cystocentesis could also be used to safely obtain a urine sample. This method can be done freehand or with a biopsy guide and is done without biopsy gel--sterile saline or alcohol is applied over the biopsy site. Insert the needle close to the transducer, keeping the needle within the plane of the ultrasound beam. After verification that the tip of the needle has advanced to the desired position within the bladder lumen, aspirate urine into the syringe (Figure 6).

  6. To prevent urine from being forced around the needle into the peritoneal cavity, avoid applying excessive digital pressure to the bladder while the needle is in the bladder lumen.

  7. On rare occasions, cystocentesis has been associated with a form of reversible collapse in cats. Although a cause-and-effect relationship has not been established, excessive vagal stimulation has been implicated. Acute bladder distention has been associated with bradycardia in humans.2 In one study, decreased heart rate induced by bladder distention only occurred in human patients with concomitant hypertension.3 Thus, excessive manipulation and compression of the urinary bladder should be avoided.

  8. To avoid aspiration of fat or abdominal contents, stop retracting the plunger before withdrawing the needle.

  9. Although blind cystocentesis (i.e., without palpating and immobilizing the bladder) has been described,4 we do not recommend it as a routine technique because of the increased risk to the patient and the potential to contaminate the sample.

  10. In most instances, prophylactic antibacterial therapy is not necessary but should be based on patient status and retrospective evaluation of the technique. Likewise, to minimize contamination of the peritoneal cavity with urine, do not apply unnecessary digital pressure to the urinary bladder during or immediately after cystocentesis (Figure 7).
II. WHAT DISADVANTAGES ARE ASSOCIATED WITH COLLECTION OF URINE BY DIGITALLY INDUCED VOIDING?
  1. Induction of micturition by application of digital pressure to the urinary bladder through the abdominal wall may be used to collect urine samples from dogs and cats.
  2. The primary advantages of this procedure are that:
    1. the risk of iatrogenic urinary tract infection and iatrogenic trauma is minimal, and
    2. urine samples may be collected from patients with distended urinary bladders at the convenience of the clinician.
  3. The primary disadvantages of this procedure are that:
    1. the urinary bladder may be traumatized if excessive digital pressure is used. This is not only detrimental to the patient; the associated hematuria may interfere with interpretation of results;
    2. the urinary bladder may not contain a sufficient volume of urine to facilitate this technique;
    3. samples are frequently contaminated with cells, bacteria, and other debris located in the genital tract, or on the skin and hair;
    4. micturition may be difficult to induce in some patients, especially male cats
    5. bladder urine contaminated or infected with bacteria may be forced into the ureters, renal pelves and kidneys. Unlike normal micturition where detrusor contraction is associated with a coordinated relaxation of voluntary and involuntary urethral sphincters, manual compression of the bladder increases intravesical pressure, but may not be associated with simultaneous relaxation of the sphincters.
III. WHAT TECHNIQUE MAY BE USED TO FACILITATE COLLECTION OF TABLE TOP URINE SAMPLES?
  1. Patients with lower urinary tract disease often have reduced bladder capacity and urge incontinence. As a result collection of urine into a cup during the voiding phase of micturition, or by cystocentesis, is difficult. Frequently small quantities of urine are voided before they can be collected.
  2. Collection of urine for analysis from smooth clean table tops with the aid of a needle and syringe may be facilitated by the use of two rectangular microscopic slides.
  3. The goal is to use the edges of the microscopic slides to form a deeper pool of urine that can more readily be aspirated.
    1. The long edges of two microscopic slides should be placed flat on the table surface so that the small sample of urine is between them.
    2. The slides should be parallel to each other, and tilted away from the urine sample at an angle.
    3. With the edges of the slides in close contact with the table, the slides should be advanced toward each other. This will cause the urine to pool along the edges of the slides.
    4. During this time, an assistant with a syringe and needle should aspirate the urine as it pools in front of the microscope slides. When the slides meet, they will form a V-shaped trough, from which most of the voided urine may be collected.
  4. Urine samples collected in this fashion are satisfactory for screening urinalysis, provided they are analyzed soon after collection. The value of the results will be influenced by the cleanliness of the table from which the sample was collected.
IV. ARE URINE SAMPLES COLLECTED BY OWNERS SATISFACTORY FOR EVALUATION?

In most situations the answer is no. Accurate assessment of laboratory tests depends on properly collected samples. Owners may collect urine in improperly rinsed containers, allow samples to dehydrate, or store samples at improper temperatures. In addition, voided urine samples may become contaminated with substances from the urethra, genital tract, digestive tract, bottom of the patient's foot, or the owner's backyard. IF owners insist on collecting urine at home, consider the following protocol:

COLLECTING URINE AT HOME


EQUIPMENT
  1. A soup ladle with a metal handle works best. Bend the handle such that it extends out further from the cup portion than usual (i.e. at a greater angle). Clean the ladle (in the dish washer, if possible); and make sure that it is dry before use.
  2. We will provide a sterile syringe and cap to store urine.
PROCEDURE:
  1. When your dog squats to urinate catch the urine in the cup of the ladle.
  2. Ideally, we do not want the initial portion of the stream. Therefore missing the first few drops is preferred. We also do not want the final portion of urine so you only need to collect what is needed.
  3. We need 5 to 10mls (1 to 2 teaspoons).
  4. Remove the syringe from its case and break the seal by pulling the plunger up one to two ml (not completely out of the syringe) and then reinsert plunger to its original starting point.
  5. Suck the urine up into the syringe.
  6. Put a black cover over the end of the syringe.
  7. Store the sample in a cool place (refrigerator, porch, ice chest). Refrigeration is not needed if the sample will be delivered in 1 to 2 hours.
  8. Bring the sample in that day or at the latest, the following day.
Voided samples are very satisfactory for routine urinalysis performed to screen patients for abnormalities of the urinary tract and other body systems. Depending on specific circumstances, however, it may be necessary to repeat analysis of a urine sample using cystocentesis. Voided samples are usually unsuitable for bacterial culture.

When possible the first part of the urine stream should be excluded from the sample submitted for analysis because it may be contaminated during contact with the genital tract, skin, and hair. In order to facilitate collection of midstream urine samples, two cups may be used to collect the sample. The portion of the sample collected in the second cup, when available, represents a midstream sample. The sample in the first cup may be discarded or used to localize hemorrhage or inflammatory disease to the urethra or genital tract. If technical difficulties or lack of patient cooperation prevent collection of the sample in the second cup, the sample in the first cup is still available for urinalysis.

URINALYSIS


I. ARE URINE REAGENT TEST STRIPS DESIGNED FOR USE IN HUMANS SATISFACTORY FOR ANIMALS?


Most diagnostic reagent strips used to perform routine urinalysis in veterinary laboratories have been designed for human use. Although these reagent strips provide useful information when used to evaluate urine samples collected from animals, test results obtained with several diagnostic urine strips are unreliable. Are you familiar with the limitations of the specific brand of diagnostic reagent strip used in your hospital? The following list summarizes limitations of most reagent strips, and suggestions to minimize them.
  1. URINE SPECIFIC GRAVITY values of dogs and cats obtained with reagent strips are usually unreliable. Because the highest value that these reagent pads can detect is 1.025 to 1.030, they are unsatisfactory to detect adequate renal concentrating capacity in dogs of cats.
    TIP: Utilize a refractometer to determine urine specific gravity values.

  2. URINE PH test pads will allow measurement of pH values to within +/- 0.5 units. This is satisfactory for routine evaluation of most patients. However these test pads will not permit precise determination of urine pH values. In addition, use care to prevent runover from the highly acidic protein test pad to the urine pH test pad to prevent a false reduction in pH.
    TIP: Utilize a pH meter to confirm results, especially when trying to measure relatively small changes in pH

  3. GLUCOSE TEST PADS contain labile enzymes ( glucose oxidase and peroxidase ). If these proteinaceous enzymes become inactive, false negative results will be obtained.
    TIP: Become familiar with the expiration date listed on the container by the manufacturer. The life of the enzymes in an unopened container may be prolonged by freezing the package. Check with the manufacturer for details.

  4. BILIRUBIN REAGENT PADS may be unreliable as screening tests in dogs because of a high percentage of false positive and false negative results in this species In contrast, positive bilirubin test results in cats are usually indicative of some underlying disease.
    TIP: Consider positive or negative urine bilirubin test results in conjunction with other clinical findings.

  5. THE OCCULT BLOOD TEST PAD may detect red blood cells, free hemoglobin, or myoglobin.
    TIP: Evaluate test results in conjunction with evaluation of urine sediment and other clinical findings.

  6. PROTEIN TEST PADS are approximately twice as sensitive to albumin compared to globulin, and three times more sensitive to albumin compared to mucoproteins. In addition, false positive results may be obtained if the urine pH is very alkaline.
    TIP: Compare questionable test results to another test method, such as the sulfosalicylic acid test. Determination of urine protein-creatinine ratios are a more reliable method to determine the magnitude of pathologic proteinuria.

  7. UROBILINOGEN TEST PADS have not been useful in the routine evaluation of canine and feline urine. A computer search of APPROXIMATELY 11,000 canine urinalysis records yielded only 0.015 positive urobilinogen tests.
    TIP: Do not rely on urobilinogen test pads to screen patients for hemolytic disorders, hepatic disorders, or patency of bile ducts.

  8. NITRITE TEST PADS used as an indirect indication of bacteriuria in humans uniformly give false negative results in dogs and cats. Available information indicates that false negative results are probably associated with interference caused by ascorbic acid normally present in canine and feline urine.
    TIP: Evaluate urine sediment and/or bacterial cultures to rule in or rule out bacterial urinary tract infections.

  9. LEUKOCYTE TEST PADS give false positive test results in most cats in absence of pyuria, and therefore are of no value in this species.
    TIP: Evaluate fresh urine sediment to determine the presence or absence of leukocytes in cats.

  10. LEUKOCYTE TEST PADS frequently give false negative test results in dogs, even when pyuria is present. Although the test is specific for WBC in dogs, it is very insensitive.
    TIP: Evaluate fresh urine sediment to determine the presence or absence of leukocytes in dogs
II. WHAT PROCEDURES SHOULD WE DO IN THE PREPARATION OF URINE SEDIMENT FOR MICROSCOPIC EXAMINATION WITH A BRIGHT-FIELD MICROSCOPE?
  1. Do collect urine specimen in appropriate container.
  2. Do refrigerate the sample if analysis cannot be performed within 30 to 60 minutes from time of collection.
  3. Do mix the specimen thoroughly, and transfer a standard volume to a conical tip centrifuge tube.
  4. Do centrifuge the sample for 3 to 5 minutes at 1500 to 2000 RPM.
  5. Do remove the supernatant with a rubber-topped disposable pipette, or by decanting, and save it for chemical analysis. Allow a standard volume (approximately 1/2 ml) of supernatant to remain in the test tube.
  6. Do resuspend the urine sediment in the remaining supernatant by agitation of the tube or "finger-flipping" of the tube.
  7. Do transfer a drop or reconstituted sediment to a microscope slide with a rubber-topped disposable pipette, and place a coverslip over it.
  8. Do subdue the intensity of the microscope light by lowering the condenser and closing the iris diaphragm.
  9. Do systematically examine the entire specimen under the coverslip with the low power objective, assessing the quantity and type (casts, cells, crystals, etc.) of sediment.
  10. Do examine the sediment with the high power objective to identify the morphology of elements, and to detect bacteria.
  11. Do record the results.
III. WHAT PROCEDURES SHOULDN'T WE DO IN THE PREPARATION OF URINE SEDIMENT FOR MICROSCOPIC EXAMINATION WITH A BRIGHT-FIELD MICROSCOPE?
  1. Don't examine a contaminated sample.
  2. Don't examine old stale urine.
  3. Don't fail to thoroughly mix the sample prior to examination.
  4. Don't allow the sediment to dry on the microscope slide.
  5. Don't use too much microscope light.
  6. Don't carelessly reconstitute the sediment following centrifugation.
  7. Don't centrifuge at excessive speeds.
  8. Don't use dirty or scratched microscope slides and coverslips.
  9. Don't use only low power or only high power magnification.
IV. WHAT CELLULAR ELEMENTS NEED TO BE DIFFERENTIATED IN URINE SEDIMENT?

The cells which can be present in urine include erythrocytes (red blood cells), leukocytes (white cells) and epithelial cells (table 3). The first rule for examining unstained urinary sediment with the microscope is to subdue the light to provide adequate contrast. The second rule is that fine adjustment should be continuously adjusted up and down to enable the viewer to see the depth of the cells and other structures that may appear clearer in a different focal plane.

Table 3. Identifying Cellular Elements in Urine

Cell Type Erythrocytea Leukocyteb
Epithelialc
Renal Tubular Transitional Squamous Neoplastic
Occurrence Common Common Rare Occasional Occasional Occasional
Shape Round (biconcave disk) Spherical Round to oblong Round, pear, spindle, caudate or polygonal Large thin plate like Variable Aberrant unusual
Contour Smooth and symmetrical Smooth Smooth to irregular Irregular Irregular. Edges may curl and fold Smooth to irregular
Color Pale yellow to clear Dull gray to pale green        
Size (microns) 6 to 7 10 to 14 10 to 50 20 to 40
Wide variation
50 Large and variable
Compared to RBC NA 1.5 to 2x 2 TO 4x 3 to 8x 10x  
Cytoplasmic features Clear Granular Fine granular Granular Clear Inclusions, atypical vacuolation,
mitotic figures
Nuclear features No nucleus Lobed or segmented, sometimes spherical Central spherical Medium often slightly eccentric Small dense Large in relation to cytoplasm, multinucleated, atypical nucleoli
Refractivity Moderate Minimal Minimal Minimal Minimal Minimal
Grouping Single Single or in clumpsd Single or in clumps Usually exfoliate in large numbers Single, but commonly in sheets of cells Single or in sheets of cells
Comments Acetic acid can be used to lyse red blood cells. By changing fine focus, red cells develop darker outline. Acetic acid can be used to accentuate the nuclei of white cells and lyse red blood cells.        

  1. The appearance of red blood cells vary depending on specific gravity and pH of urine. In concentrated urine they usually appear smaller, crenated and distorted.
  2. White cells rapidly lyse in alkaline and hypotonic urine (up to 50% lysed in 1 hour at room temperature or in 2 hours at refrigeration temperature).
  3. It is difficult to accurately distinguish between epithelial cells that arise from the various parts of the urinary tract. For this reason, laboratories often report the presence of epithelial cells without attempting to differentiate them.
  4. Clumps of white cells alter the number counted, and therefore should be reported.
V. IS THE URINALYSIS SUFFICIENT TO DIAGNOSE BACTERIAL URINARY TRACT INFECTION?

Bacteria are usually not detected by urine sediment examination until concentrations exceed at least 10,000 organisms per milliliter of urine (100,000 10,000 organisms per milliliter for coccal organisms). Likewise, the number of leukocytes in urine is variable and may be blunted in patients with hyperadrenocorticism, those receiving corticosteroids, those producing alkaline urine, and those producing dilute urine. Bacteria may be falsely indentified in urine sediment viewed with stains that have become contaminated with bacteria or with stains that contain precipitated debris.

To ensure appropriate diagnosis and treatment, culture urine for aerobic bacteria when diagnosing or monitoring bacterial urinary tract infection.

VI. WHAT URINALYSIS RESULTS ARE ASSOCIATED WITH LIFE THREATENING DISEASE REQUIRING THAT THE VETERINARIAN BE NOTIFIED IMMEDIATELY?


The speed and economy with which life-saving information can be obtained with simple laboratory equipment supports the usefulness of the urinalysis in the emergency setting. For these reasons, we include urinalyses as a part of the initial evaluation of all patients with illnesses of unknown causes that require hospitalization. The following table (Table 4) lists urinalysis abnormalities and their associated diseases that may require urgent diagnostic and therapeutic consideration.

Table 4

Urine Abnormality Associated Disorder usually requiring urgent
diagnostic and therapeutic consideration
Glucosuria Diabetes mellitus
Acute renal failure
Acute pancreatitis
Ketonuria Uncontrolled diabetes mellitus
Bilirubinuria (cats) Liver disease
HemoglobinuriaIntravascular hemolysis (immune-mediated hemolytic anemia,
onion toxicity, zinc toxicity)
WBC casts Bacterial Pyelonephritis
Bacteriuria Bacteremia
Pyelonephritis
Prostatitis
Pyometra
Calcium oxalate crystalluria Ethylene glycol toxicity
Hypercalcemia
Urinary obstruction with uroliths
Urate crystalluriaHepatic encephalopathy/portosystemic shunt
Urinary obstruction with uroliths that are radiolucent
by survey radiography
Neoplastic epithelial cellsUrinary tract neoplasia


SELECTED REFERENCES

BOOKS:


Urinalysis: a Clinical Guide to Compassionate Patient Care. By Carl A Osborne and Jerry B Stevens, Published by Bayer (Veterinary book with many good pictures and explanations)

A Handbook of Routine Urinalysis by Sister Laurie Graff, J.B. Lippincott Company, (Book directed for analysis of human urine, but has many good explanations and pictures).

ARTICLES:


Comparison of normal urine samples collected by cystocentesis with and without priori skin disinfection. Fry DR, Holl, Holloway SA. Aust Vet Pract 34:2-5, 2004.

Severe bradyarrhythmia in a patient with Alzheimer's disease and a patient with cerebral ischemia, both induced by acute distension of the bladder. Koch HJ, Szecsey A, Raschka C. Int J Clin Pract 55:323-5, 2001.

Baroreceptor-heart rate sensitivity enhancement after urinary bladder distension in essential hypertensives. Bardelli M, Siracusane S, Comminotto F, et al. Urological Res 27:153-156, 1999.

Step by step performing cystocentesis. Royer N. Vet Tech 18:298-299, 1997.

Needle-tract implantation following US-guided fine-needle aspiration biopsy of transisitional cell carcinoma of the bladder, urethra, and prostate. Nyland TG, Wallack ST, Wisner ER. Vet Radiol Ultrasound 43:50-53, 2002.




Urolithiasis: Stone identification and Management
Part 1 & 2

Detection of uroliths is not always justification for their management. The need for urolith removal and the type of therapy depends on the effects of the urolith on the patient (asymptomatic, recurrent infection, dysuria, urinary obstruction), the characteristics of the urolith (mineral composition, size, contour, number, and location), and the familiarity of removal techniques, and availability of equipment to the veterinarian (table 2). For example, with additional training and newer technological advances (cystoscopy and lithotripsy), surgical urolith removal is becoming less desirable for both the patient and client. The following describes strategies to predict mineral composition and several novel methods of urolith management that are much less invasive than surgery.

Predicting Mineral Composition


Accurate predictions of the mineral composition of uroliths allow veterinarians to develop rational therapeutic plans with a reliable outcome. This prognostic information is essential to veterinarians in the event that additional testing is needed before surgical urolith removal. For example, should serum concentrations of bile acids be evaluated in a cat with probably urate uroliths? It may be important if anesthetic agents require hepatic elimination or if post-surgical analgesics are potentially toxic to the liver. This information is also essential to clients so that they can understand therapeutic options for urolith removal. For example, medical dissolution is an effective, non-invasive method for eradication of uroliths composed of Struvite.

When predicting mineral composition of uroliths many factors can be used. Some veterinarians rely primarily on crystalluria patterns from urinalysis results to make their decision. Although crystal type is helpful, in many cases crystals are not detected. Because cats have a great capacity to concentrate their urine, several types of crystals easily precipitate as urine becomes cooler than body temperature. As I have managed urolith patients over the years, I have recognized some helpful generalities. Crystalluria is either absent or the type detected is not in agreement with mineral composition in more than 50% of the cases. In one study of 30 cases of struvite urocystoliths, struvite crystals were only detected in 17 patients (Osborne 1990). If I were to choose a single test to predict mineral composition of uroliths, it would be their radiographic characteristics (table1). Predicting mineral composition from survey radiographs may be more reliable because multiple pieces of information are gathered from a single glimpse. The degree of radio-opacity, urolith size, number of uroliths, urolith contour, and location provide valuable clues to their composition. This in combination with urolith prevalence (figure 1) will allow accurate prediction of uroliths prior to their submission for quantitative mineral analysis. For example, multiple small very radio-opaque uroliths are likely to be composed of calcium oxalate because radio-opaque calcium phosphate uroliths are rare. The most common uroliths in the upper urinary tract of cats are also commonly composed of calcium oxalate (figure 2).


TABLE 1. Predicting Mineral Composition of Uroliths Based on Radiographic Appearance


MineralRadiographic density
compared to soft tissue
Surface contour Shape Usual Number Approximate
Size
CaOx +++ to ++++ Speculated to smooth Commonly round >5 1 to 4mm
Sterile MAP ++ to +++ Smooth Round or disk 1 to 3 2 to 7mm
Infection MAP + to +++ Smooth Round to faceted Few to many 2 to 7mm
Urate - to ++ Smooth Round to oval 2 to 5 2 to 4 mm
CaP +++ to ++++ Smooth Round to faceted Few to many 1 to 4 mm
Cystine - to +++ Smooth Round to faceted Few to many 2 to 4 mm
Silica ++ to ++++ Radial projections rare 2 to 4 mm

CaOx = calcium oxalate CaP=calcium phosphate, MAP = magnesium ammonium phosphate.








Managing Uroliths in the Lower Urinary Tracts of Cats


Detection of uroliths does not mandate their removal. For example, to minimize the number of surgeries in male cats with asymptomatic recurrent uroliths, it may be prudent to wait until cats develop clinical signs. Owners of these cats need to be appraised of the clinical signs and potential consequences of a urethral obstruction. However, if uroliths are sufficiently large or irregular such that an obstruction is less likely the probability of a life-threatening complication is low.

To minimize subjecting cats to invasive procedures consider going through a series of questions to develop a logical approach to urolith removal (Table 2):


TABLE 2. Methods of Urolith Removal
(Least Invasive to Most Invasive)

Method Suitable application Considerations
Spontaneous voiding Small (< 3 to 5mm), asymptomatic urocystoliths Patients with uroliths larger than the urethral lumen may develop urethral obstruction
Concomitant UTI should be eradicated
Medical Dissolution Sterile Struvite and infection-induced Struvite. Also see our website: http://www.cvm.
umn.edu/depts/minnesot
aurolithcenter/home
Sterile Struvite uroliths dissolve within weeks
Large infection induced Struvite stones may take 2 to 3 months to dissolve
Voiding urohydropropulsion (VUH-Table 3) To evacuate small to moderate size (<2 to 4mm) urocystoliths of any composition Not suitable for male cats unless they have a perineal urethrostomy
Not suitable for patients with a urethral obstruction
Not ideal for patients that have recently undergone bladder surgery
Eradicate urinary infection prior to performing VUH.
Stone Basket Retrieval Urocystoliths smaller than (<3 to 5mm) the distended diameter of the urethra Not suitable for male cats unless they have a perineal urethrostomy
Performed during cystoscopy.
Stone retrieval baskets are delicate and break easily.
Intracorporeal Lithotripsy (laser, ultrasonic, or ballistic) Urocystoliths in females Performed during cystoscopy
The urethra of the male cat will rarely accommodate cystoscopy equipment to perform lithotripsy.
Extracorporeal shock wave lithotripsy
(ESWL)
Nephroureteroliths The ability to perform ESWL without damaging feline kidneys is controversial-newer generation lithotriptors may prove safer
Cystotomy/ Urethrotomy/
urethrostomy
Urocystoliths or uroliths lodged in the urethra Consider retrograde urohydropropulsion of urethroliths prior to urethral surgery
Cystotomy- failure to remove all uroliths in 15-20% of cases
Ureterotomy/ Ureteroneocystotomy/ Ureteroneoureterotomy Clinically active ureteroliths High degree of surgical skill required when performed on cats
Surgery performed on dilated ureters has been associated with greater success than normal sized ureters
Pyelotomy/
nephrotomy
Nephroliths Some reduction in kidney function should be anticipated following surgery


Question 1. Are stones composed of Struvite?

Uroliths composed of magnesium ammonium phosphate (Struvite) can be dissolved medically with a high degree of success (Osborne 1990, Houston 2004). Typically, sterile Struvite uroliths dissolve in 2 to 4 weeks with diets that provide reduced quantities of magnesium and phosphate and promote acidification of urine. When formation of Struvite stones results from urinary tract infection caused by urea-splitting bacteria, dissolution time is typically longer. When managing infection-induced Struvite uroliths, remember that in addition to special diets, appropriate antimicrobics are necessary throughout the entire period of dissolution. It is important to recognize that uroliths located in the urethra are less likely to dissolve because they are not continually surrounded by urine that is undersaturated for magnesium ammonium phosphate. Therefore, urethroliths need to be flushed back into the urinary bladder and their position periodically monitored to improve success of dissolution therapy.

Question 2. Is the urolith-former a female?


Once all cats with Struvite uroliths have been managed medically, female cats with non-Struvite uroliths have an advantage over males. This is not because urate uroliths cannot be dissolved medically (I have dissolved urate uroliths in a few cats with allopurinol (15mg/kg q 24 hr) and lower protein diets that do not promote urine acidification), but because the size of the urethra in the female permits manipulation of uroliths without the need of a surgical incision.

Question 2a. Are uroliths less than 3 to 4mm in diameter?


If the answer is yes, urolith removal is usually amenable to either voiding urohydropropulsion (table 3) or basket retrieval. Although, I developed voiding urohydropropulsion, I find basket retrieval much easier, more efficient, and less traumatic. This may be related in part to the small volume of the feline bladder. To effectively expel uroliths by voiding, sufficient volume of fluid is needed to propel uroliths. Likewise, the propensity for obesity in cats makes in more difficult to locate and express the urinary bladder.


TABLE 3. Performing Voiding Urohydropropulsion

1. Anesthetize the patient They type of anesthesia selected may vary based on the likelihood of success and gender of the patient. Consider reversible short acting anesthetics (e.g. Propofol) for patients with very small uroliths that are easily removed. Patients likely to go to surgery/lithotripsy should be placed under inhalation anesthesia.
2. Attach a 3-way stopcock to the end of the urinary catheter The 3-way stopcock facilitates control of the volume of fluid entering the bladder and containment of fluid once the bladder is filled.
3. Fill the urinary bladder Sterile physiologic solutions (LRS, normal saline) are injected through a transurethral catheter to distend the bladder. If fluid is expelled prematurely around the catheter prior to adequate bladder distension, the vulva and/or urethra can be gently occluded using your thumb and first finger. Placement of additional fluid may not be needed.
4. Position the patient such that the spine is approximately vertical Repositioning the patient allows uroliths to accumulate at the neck of the bladder facilitating their expulsion. Anatomically, the urethra does not become vertical until the caudal spine is 20 to 25 degrees anterior of vertical, but this may not be clinically important to evacuate uroliths.
5. Agitate the bladder Agitating the urinary bladder left and right is performed to dislodge uroliths loosely adhered to the bladder mucosa.
6. Express the urinary bladder Apply steady digital pressure to the urinary bladder to induce micturition. Once voiding begins, the bladder is more vigorously compressed. Compress the urinary bladder dorsally and cranially (toward the back and head of the patient). Movement of the urinary bladder caudally toward the pelvic canal may cause the urethra to kink preventing maximal urethral dilation.
7. Repeat steps 2 through 6 The bladder is flushed repeatedly until no uroliths are expelled.
8. Medical Imaging Radiography provides an appropriate method of assessing successful expulsion of uroliths. To enhance detection of remaining small uroliths consider a double-contrast cystography (only the lateral view is needed).


Basket Retrieval of Uroliths

Retrieving stones cystoscopically with a stone basket is ideal for removing small stones from the urinary bladder. It is a relatively simple technique. It can be performed in patients who recently had a cystotomy to remove stones that were not completely removed. Its limitation, however, is that stones must be small enough such that they can be pulled through the urethra. A variety of stone baskets are available to facilitate this technique (Stone Retrieval Grasping Forceps, Boston Scientific, Natick MA and N-CircleŽ Nitinol Tipless Stone Extractor, Cook Urologic Inc, Spencer, IN).

Question 2b. Are uroliths larger than 4 to 6mm in diameter?


As uroliths become larger the opportunity for minimally invasive techniques diminishes. Laser lithotripsy can be utilized to fragment uroliths into pieces that can and retrieved through the urethra. However, laser lithotripsy is only offered at a few specialty practices in North America. Until laser lithotripsy becomes more widely available, it is likely that cats will undergo surgical urolith removal.

Intracorporeal Laser Lithotripsy


Several forms of energy (electrohydraulic, ultrasonic, and ballistic) can be delivered through a cystoscope to fragment uroliths in the bladder and urethra of cats. Each device has its advantages and disadvantages (table 1). Because of the versatility of laser lithotriptor and the authors' familiarity with laser lithotripsy, the remaining discussion applies to Holmium:YAG laser lithotripsy in companion animal practice for the fragmentation of urocystoliths and urethroliths.

The term "laser" is an acronym for "Light Amplification by Stimulated Emission of Radiation" A laser is a device which transmits light of various frequencies into an extremely intense, small, and nearly nondivergent beam of monochromatic radiation in the visible region with all the waves in phase. Lasers are capable of mobilizing immense heat and power when focused in close range.

Use of laser energy for intracorporeal lithotripsy is a relatively new concept. In 1968, investigators first reported in vitro fragmentation of uroliths with a ruby laser. However, because fragmentation of stones was associated with generation of sufficient heat that would likely damage adjacent tissues, it could not be used to treat patients. Likewise, use of carbon dioxide laser energy was considered to be unsuitable for clinical use because it could not be delivered through nontoxic fibers. However, in 1986 researchers using a 504 nm, pulsed dye laser successfully and safely treated human patients with ureteroliths. The holmium: YAG laser is the newest device available for clinical lithotripsy.

The mechanism of stone fragmentation with the Holmium:YAG laser is mainly photothermal, and involves a thermal drilling process rather than a shock-wave effect. Ho:YAG laser energy is transmitted from the crystal to the urolith via a flexible quartz fiber. To achieve optimum results, the quartz fiber tip must be guided with the aid of a cystoscope so that it is in direct contact with the surface of the urolith. After uroliths have been sufficiently shattered such that they are small enough to pass through the urethra, fragments can be removed using a stone basket or voiding urohydropropulsion.

Question 3. Is this a Male cat with a non-Struvite Urolith?


Male cats have not been afforded the same advantages as females. Because of the small size of the urethra, most will have uroliths removed surgically. With the desire to manage all uroliths non-surgically, some have incorporated minimal surgical techniques were the urinary bladder is accessed through small celiotomy incisions. It is also likely that extracorporal shock wave procedures once refined can fragment urocystoliths to sizes that are unlikely to become trapped in the urethra.

Preventing Urolith Recurrence


Prospective studies evaluating the biologic behavior of uroliths in cats have not been published. However, the following results were obtained from a retrospective study performed at the University of Minnesota (Hasan 2006). In 1998, uroliths from 4760 cats were submitted to the Minnesota Urolith Center for quantitative mineral analysis. The Center's database was searched for urolith resubmissions from the same patients over the next 5 years. In 1998, 2393 cats were diagnosed with calcium oxalate uroliths. Recurrence was detected in 7.1%, 0.6% had a second recurrence and 0.1% had a third recurrence; mean recurrence times were 23, 38, and 48 months, respectively. In 1998, 1821 cats were diagnosed with Struvite uroliths. Recurrence was detected in 2.7%. 0.2% had a second recurrence; mean recurrence times were 27 and 40 months, respectively. Urolith recurrence rate was 1.6 times higher in females than males. In 1998, 221 cats were diagnosed with urate uroliths. Recurrence was detected in 10.9 %. 2.3% had a second recurrence; mean recurrence times were 20 and 41 months, respectively. Urolith recurrence rate was 1.8 times higher in females than males. Because some uroliths associated with recurrent episodes may not have been submitted to the Minnesota Urolith Center, these results may underestimate the actual urolith recurrence rate.

Likewise, prospective studies assessing therapeutic intervention have not been evaluating in urolith-forming cats. Without this information, recommendations have been extrapolated from other species. The goals of dietary prevention include 1) reducing calcium concentration in urine, 2) reducing oxalate concentration in urine, 3) promoting a high concentration of and high activity of inhibitors of calcium oxalate crystal growth and aggregation in urine, and 4) maintaining a less concentrated urine. (Osborne 1996). New studies have indicated that although hydrocholorthiazide (1mg/kgq12hr) decreased urine saturation for calcium oxalate in healthy cats, their urine concentration of calcium did not change (Hezel 2007). Since dietary strategies effectively dissolve Struvite uroliths, similar strategies shoud be be equally effective and preventing Struvite uroliths. To minimize the risk of urate urolith formation, we recommend feeding diets with reduced quantities of purines. Likewise, diets should not be formulated to promote formation of highly acidic urine. Since amino acids provide nitrogen and carbon for endogenous production of purines, it is desirable to restrict dietary protein to maintenance levels. In addition to reducing dietary protein, consider diets formulated from nutrient sources derived from low purine foods (table). The need for xanthine oxidase inhibitors such as allopurinol is unknown. Because of the potential for adverse side effects (gastrointestinal upset, skin rashes, leukopenia, thrombocytopenia, hepatitis and kidney failure), we reserve the use of allopurinol (5 to 10mg/kg) for cats with highly recurrent disease.


Table 4. Relative Purine Content of Foods

  Foods to Avoid
(High Purine Content)
Foods to use sparingly
(Moderate purine content)
Foods Permissible to feed (Negligible purine content)
Fish Anchovies, Herring, Mackerel, Mussels, Roe, Sardines, Scallops, oysters Fish and shell fish not listed in the foods to avoid  
Meats Organ Meats (brains, heart, kidney, liver)
Game meats (duck, goose) Meat broths
Chicken, beef, lamb, pork Gelatin
Fruits and Vegetables   Beans, cauliflower, green peas, lentils, mushrooms, cauliflower, lentils, spinach Nuts, and fruits and vegetables not listed in the other two columns.
Egg/Dairy   Oats, wheat germ Eggs, cheese, milk, ice cream, butter,
Pasta /Rice   Whole grain breads and cereals Rice, pasta, Macaroni, breads cereals from refined grains,
Miscellaneous Baker's and Brewer's Yeast    


References

Hasan A, Osborne CA, Lulich JP, et al. Urolith recurrence in cats. J. of Veterinary Internal Medicine 2006;20:786.

Hezel A, Bartges JW, Kirk CA, et. al. Influence of hydrochlorothiazide on urinary calcium oxalate relative supersaturation in healthy young adult female domestic shorthaired cats. Veterinary Therapeutics 2007;8:247-254.

Houston DM, Rinkardt NE, Hilton J. Evaluation of the efficacy of a commercial diet in the dissolution of feline struvite bladder uroliths. Veterinary Therapeutics 2004;5:187-201.

Osborne CA, Lulich JP, Thumchai R, et.al. Diagnosis, medical treatment, and prognosis of feline urolithiasis. Vet Clin N Amer. 1996; 26:589-627.

Osborne CA, Lulich JP, Kruger JM, et.al. Medical dissolution of feline struvite urocystoliths. JAVMA 1990;196:1053-1063.



Safely Managing Urethral Obstruction in Cats

Obstructive urethropathy is commonly caused by intraluminal precipitates (matrix-crystalline urethral plugs and uroliths). However, other diseases in addition to concomitant swelling of the urethral wall and spasm of urethral musculature may contribute to difficult urine expulsion. Following diagnostic evaluation to determine a cause, we recommend a step-by-step procedure (table 1) when attempting to restore urethral patency of an obstructed male cat. Table 1 several techniques to clear the urethra of intraluminal obstructions. Decompressive cystocentesis is recommended in the retropulsion of urethroliths. The first two can be performed to clear crystalline mucous plugs and do not require that decompressive cystocentesis be performed. The third technique (Retrograde Flushing of the Urethral Plug) can be used to clear the urethra of urethral plugs and uroliths. Decompressive cystocentesis should be performed prior to occluding the external urethral orifice around the urethral catheter.

TABLE 1. TECHNIQUES TO REMOVE URETHRAL PLUGS FROM MALE CATS
  1. Perform appropriate diagnostics (medical imaging) to insure that other causes of urethral obstruction have been eliminated (e.g., uroliths, cancer, and stricture).
  2. Insure that patient is suitably prepared for anesthesia (e.g., normothermic, normotensive, normokalemic, the urinary bladder has been decompressed, etc.)
  3. Administer appropriate and sufficient anesthesia to abolish urethral pain and facilitate urethra manipulation
  4. Make every effort to protect the patient from iatrogenic complications associated with urethral catheterization (trauma, perforation, infection).
Normograde Evacuation of Plug
  1. Exteriorize the penis and massage the urethra with the goal of disrupting the continuity of the urethral plug.
  2. Provide steady, but not excessive pressure on the urinary bladder to evacuate the plug. Avoid excessive pressure because it may result in trauma to the bladder wall, reflux of potentially infected urine into the ureters, and/or rupture of the bladder wall.
  3. Submit plug for quantitative mineral analysis and histopathologic evaluation.
Normograde Evacuation of Plug Following Reverse Flushing of Fluid
  1. Exteriorize penis and massage urethra with the goal of disrupting continuity of the urethral plug.
  2. Select a urethral catheter (e.g. olive tip or Tom cat catheter) for initial urethral catheterization. Attach catheter to an intravenous collection set and syringe filled with normal saline. Evacuate air form the line by flushing the system with the saline from the syringe.
  3. Before inserting the catheter, stretch the exteriorized penis caudally and dorsally (i.e., parallel with the spine).
  4. Without using excessive force, advance the catheter to the site of obstruction.
  5. Flush large quantities (100 ml) of physiologic saline into the urethral lumen allowing it to reflux out of the external urethral orifice. As the plug is disrupted, cautiously advance catheter toward the urinary bladder.



The beneficial effects of flushing without occlusion of the urethra around the catheter is that a portion of the matrix crystalline plug can be flushed out of the external urethral orifice.
  1. Apply steady, but gentle digital pressure to the bladder wall attempting to expel urethral plug out of the external urethral orifice. Excessive pressure should not be used because it may result in trauma to the bladder wall, reflux of potentially infected urine into the ureters, and/or rupture of the bladder wall.
  2. Submit plug for quantitative mineral analysis and histopathologic evaluation.
TABLE 1. TECHNIQUES TO REMOVE URETHRAL PLUGS FROM MALE CATS

Retrograde Flushing of the Urethral Plug
  1. Attempting normograde evacuation of plug using reverse flushing techniques (see above) is likely to facilitate retrograde movement of urethral plugs in to the urinary bladder.
  2. If the bladder is even moderately over-distended perform decompressive cystocentesis* using a 22gauge, 1.5 inch needle attached to an intravenous collection set, 3-way stop cock and syringe.
  3. Select a short olive-tip urethral catheter. Attach catheter to an intravenous collection set and syringe filled with normal saline. Evacuate air form the line by flushing the system with the saline from the syringe.
  4. Before inserting the catheter, stretch the exteriorized penis caudally and dorsally (i.e. parallel with the spine).
  5. With the catheter in place, occlude the urethra around the catheter shaft using your finger and thumb. Placing a moistened gauze pad between the urethra and your fingers may minimize trauma to the surface of the urethra. By preventing reflux of solutions out of the external urethral orifice, this maneuver tends to dilate the urethra and advance the plug into the urinary bladder.
  6. Stretch the urethra caudally as physiologic saline is flushed.
Flushing of the Urethral Plug for Veterinarians Uncomfortable Performing Decompressive Cystocentesis
  1. Attempting normograde evacuation of plug using reverse flushing techniques (see above) is likely to facilitate retrograde movement of urethral plugs in to the urinary bladder.
  2. Consider using a Tom Cat catheter. Attach catheter to an intravenous collection set and syringe (20 to 35ml) filled with normal saline. Evacuate air form the line by flushing the system with the saline from the syringe.
  3. Before inserting the catheter, stretch the exteriorized penis caudally and dorsally (i.e. parallel with the spine).
  4. Place the catheter insider the urethral lumen to the site of obstruction. With the catheter in place, vigorously flush fluid through the urethral lumen without occluding the urethra around the catheter shaft. The goal is to flush fragments out of the distal urethral allowing the catheter to be slowly advanced without damaging the urethra. Because the urinary bladder is over distended, we assume that most material and the retropulsion fluid will be forced from the urethra.
  5. As the urethra is cleared, the catheter is slowly and cautiously advanced forward into the urinary bladder.
* Advantages of decompressive cystocentesis:
  • Appropriate sample for urinalysis and culture
  • Reduce discomfort and pain associated with bladder over-distension
  • Reduce biochemical consequences of obstruction (e.g., acidemia, hyperkalemia, azotemia, etc.).
  • Decreased resistance to urethral retrograde flushing





    Figure 1. Dissolving struvite uroliths; MAP = magnesium ammonium phosphate (struvite); CaOx = calcium oxalate; UTI = urinary tract infection


  • © 2009 - Jody P. Lulich, DVM, PhD, DACVIM - All rights reserved