Problem Definition and Recognition

Urine normally appears as varying shades of yellow to amber. The depth of color is related to urine volume. Dark urine does not necessarily mean concentrated urine although very pale urine is most frequently associated with minimally concentrated urine. Both endogenous and exogenous pigments can contribute to the color of urine. Normally, urochrome and urobilin are the endogenous pigments that determine urine color in conjunction with urine volume and concentration. A variety of disorders may cause variations in urine color due to endogenous pigments associated with bilirubin, hemoglobin, and myoglobin. Exogenous pigments associated with drugs, food dyes, toxins, or microbes may also influence urine color. Urine pigments are initially assessed by dipstick colorimetric testing (DSCT) and by specific gravity with a refractometer or hydrometer. These diagnostic procedures combined with examination of urine sediment are the primary techniques required to complete Figure 33-1, an algorithm designed to assist in diagnosing the cause of discolored urine in the dog and cat. The reader is referred to subsequent sections in this chapter for more specific discussion regarding the diagnosis of disorders associated with red, brown, and miscellaneous urine colors.

FIGURE 33-1. Algorithm for the diagnosis of red or brown urine.

Red Urine

Figure 33-1 includes a diagnostic plan for finding the basic cause of red urine. The initial step requires the collection of a urine sample and analysis for occult blood by DSCT. The occult blood test will be positive for RBCs, hemoglobin, and myoglobin and negative for red pigments such as porphyrins, pyridium, or red dyes in some dog foods. The urine sample is centrifuged and the supernatant and sediment are tested for occult blood. The sediment is also examined microscopically for RBCs. A positive occult test on the sediment with the presence of RBCs in the sediment confirms the presence of hematuria. A negative occult reaction in the sediment coupled with the absence of RBCs suggests that hemoglobin or myoglobin is present. Inspection of the patient’s plasma can be helpful in distinguishing hemoglobin from myoglobin. Plasma that appears pink to red is supportive of hemoglobinuria, while clear plasma is compatible with myoglobinuria or lysis of RBCs in the urine prior to sediment examination.

Hematuria

Hematuria, defined as the presence of RBCs in the urine, frequently occurs in dogs and cats. Hematuria can be undetectable on gross inspection of urine samples or can impart a variety of colors to urine such as red, orange, or brown, which must be distinguished from other components that cause urine discoloration. In healthy animals, RBC excretion in urine is about 3,000/minute, which amounts to less than two to four RBCs per high-power field in the urine sediment. Determining the source of hematuria can be challenging since RBCs can be introduced anywhere along the urogenital tract. Due to the numerous potential causes for hematuria (Table 33-1) a systemic diagnostic plan must be followed to make an accurate diagnosis.

Diagnostic Plan. There are three steps in the diagnostic plan for the problem of hematuria: (1) collection of the initial database, (2) localization of hematuria to an anatomic site, and (3) identification of the cause. Figures 33-2 and 33-3 show algorithms for the diagnosis of hematuria in the presence and absence of dysuria.

The Initial database. The initial database includes a medical history, complete physical examination, observation of micturition, and analysis of the urine. The initial database will detect hematuria, help localize the site of bleeding, and help dictate further diagnostic procedures.

Historical information should include duration and severity of hematuria; at what stage blood appears during urination; the presence of other urinary tract signs such as dysuria, stranguria, or pollakiuria; any medication the patient may be taking; and potential exposure to toxins. Additional information such as reproductive history; incidents of trauma, recent vigorous exercise, or previous illness; observation of bleeding unrelated to the urinary tract; and the presence of signs of systemic disease may also aid in the diagnostic process. Owner’s observations should be verified by the clinician whenever possible.

A complete physical examination should be performed. Observation of the patient in the act of micturition is an important part of the examination since the presence of hematuria can sometimes be confirmed and clinical signs may be identified, which can help localize the source of hematuria (see subsection “Localization of Hematuria to an Anatomic Site”). Particular attention should be given to inspection of the genitalia and urethral orifice as well as palpation of the kidneys, bladder, and prostrate. The uterus of the intact female dog or cat is often not palpable unless enlarged or associated with a mass. Detection of abnormalities in the bladder wall or lumen may be enhanced by palpating the bladder shortly after voiding. The penis or vagina should be thoroughly examined for evidence of bleeding, trauma, or tumors. More thorough examination of these structures can be accomplished by extruding the penis from the prepuce and using a speculum and/or digital palpation to assess the vagina. In addition, urogenital examination should include digital palpation of the perineal urethra and rectal palpation to evaluate the pelvic urethra, prostate, and caudal aspect of the bladder. Urethral catheterization may be indicated in some cases to evaluate patency of the urethra. The patient should be carefully searched for evidence of a generalized coagulation problem such as petechiation of the skin or mucous membranes. Ocular fundic examination should also be performed to identify any evidence of systemic disease.

TABLE 33-1. Causes of hematuria in dogs and cats classified by anatomical site of origin

DIC, disseminated intravascular coagulation.

A urinalysis is performed early in the evaluation process since subsequent diagnostic procedures are predicated in many cases by these findings. Urine collection techniques may affect the presence and amount of blood in the urine. The method of urine collection and urine specific gravity should always be taken into consideration when evaluating urine samples. Performing an initial urinalysis using a midstream voided sample offers the advantage of nontraumatic collection. However, blood, bacteria, and white blood cells may be contributed to urine by disease in the genital tract, and these findings may be confused with urinary tract disease. Collection of urine by catheterization or manual expression is not encouraged, since catheterization invites infection and some trauma, whereas manual expression usually produces some hematuria and is technically difficult in males. Iatrogenic hematuria is often minimal when urine is collected by cystocentesis with a 22-gauge needle.

FIGURE 33-2. Algorithm for the differential diagnosis of hematuria in patients with dysuria. FNA, fine-needle aspirate.

FIGURE 33-3. Algorithm for the differential diagnosis of hematuria in patients without dysuria. EU, excretory urogram; UP/UC, urine protein to creatinine ratio.

Urine specimens should be examined within 30 minutes after collection since longer delays in analysis can result in deterioration of cellular content, including RBCs. Delaying analysis can also cause pH changes, promote bacterial growth, and lead to the formation of precipitates that can be confused with crystals (Chew and DiBartola 1998). Refrigeration of urine minimizes these alterations in content when examination must be delayed. However, chemical analysis by DSCT can be altered when the urine sample is chilled and is best performed prior to refrigeration of the sample or after the refrigerated sample has been gradually warmed to room temperature.

When evaluating the initial database, keep in mind that extraurinary factors can initiate episodes of hematuria, including congestive disorders such as heart failure, toxins or infectious disease resulting in coagulopathies, and events such as vigorous exercise.

Localization of Hematuria to an Anatomic Site. Animals with gross hematuria can be divided into two groups, depending on the presence or absence of dysuria, stranguria, and pollakiuria. The presence of any of these signs indicates disease of the bladder, urethra, prostate, or vagina. When dysuria/stranguria is absent, disease of the kidney, ureter, or uterus is suspected.

Although variable to some degree, the stage of micturition at which blood appears can also aid in localizing the origin of hematuria. Hematuria at the beginning of micturition or dripping independent of urination suggests disease of the prostate, urethra, penis, uterus, or vagina. Blood produced at the end of urination frequently indicates urinary bladder origin. Blood that is present throughout urination indicates disease of the kidney, ureter, bladder, or reflux of prostatic discharge into the bladder. Comparing the results of urinalysis from an initial midstream voided sample with one from a subsequent cystocentesis sample can sometimes help localize the source of hematuria. When hematuria is detected in the voided sample but is absent in the cystocentesis sample, disease of the urethra or genital tract is indicated.

Coagulopathies or trauma can cause bleeding to develop anywhere along the urogenital tract. When hematuria appears to be associated with a coagulopathy, examining the patient for evidence of concurrent urogenital disease is still advisable. Signs of systemic disease such as weight loss may indicate that the source of hematuria is associated with the upper urinary tract or genital tract structures such as the prostate. Prostatic disease may also be indicated in male dogs with hematuria that exhibit straining when defecating. Hematuria of upper urinary tract origin may be suggested in some situations as a result of the patient’s medication history or the pet’s potential exposure to toxins.

Identification of the Cause of Hematuria

Following the procedures outlined in Figure 33-2 or 33-3, a clinical diagnosis is made following completion of radiographic, ultrasonographic, cytologic, microbiologic, and endoscopic procedures. These procedures together with ancillary tests such as a coagulation profile or blood pressure evaluation comprise the expanded database for the problem of hematuria. Table 33-2 lists the various causes of hematuria and characterizes them relative to clinical findings.

A laboratory database consisting of a CBC, biochemistry profile, and urinalysis is appropriate for all patients with hematuria. Aspects of urinalysis have been discussed in an earlier section. The platelet count/estimate and RBC count can help identify the presence of coagulopathy or factors such as anemia that may relate to severity or treatment of hematuria. Biochemistry profile abnormalities such as azotemia can indicate a renal source of hematuria and alert the practitioner to potential complications in pursuing diagnosis and treatment. If a coagulopathy is suspected, additional laboratory tests such as a coagulation profile or von Willebrand’s factor activity may be indicated.

Diagnostic imaging is often a valuable tool in identifying the source of hematuria. Radiographs, contrast studies, and ultrasonography can reveal irregularities, masses, and uroliths associated with the urogenital tract. Ultrasonography also provides the opportunity to obtain fine-needle aspirates and biopsies in a safer and more precise manner.

Rigid and flexible endoscopy of the lower urinary tract can be a useful diagnostic procedure in many hematuria cases. Cystourethroscopy gives the opportunity for identification and localization of lesions, biopsy and culture of tissues with greater precision and safety, and expansion of therapeutic options. Urinary tract endoscopy offers the unique opportunity to directly visualize blood coming from one or both kidneys via the ureteral openings into the bladder. Rigid endoscopy is generally limited to female dogs and cats weighing more than 3 kg and less than 20 kg, while flexible endoscopy can be used in the majority of cats and dogs regardless of size or gender (McCarthy 2002; Chew et al. 2003).

In some cases, more invasive methods such as abdominal exploratory surgery may be necessary to identify and/or correct the source of hematuria. Performing a coagulation profile in patients with hematuria should be considered prior to undertaking exploratory surgery or biopsy.

It should be remembered that neoplasia can occur anywhere along the urogenital tract, be benign or malignant, and be primary or metastatic. Presumed neoplastic changes can be confused with other disorders, including such entities as granulomas, prostatic hyperplasia, and urethral prolapse in the male.

Hemoglobinuria

Hemoglobinuria is the presence of free hemoglobin in urine, arising from two basic sources: (1) hemoglobin filtered by the glomeruli and (2) hemoglobin released by the lysis of RBCs in dilute urine or aged urine. These two causes of hemoglobinuria are differentiated by examining the urine sediment for RBCs (hematuria causing hemoglobinuria). In this section, true hemoglobinuria is discussed.

Causes. Hemoglobin is a metalloprotein of molecular weight 64,500 and is barely small enough to pass the glomerular filter. True hemoglobinuria is caused by the intravascular destruction of RBCs with hemoglobin released into the plasma. When intravascular hemolysis is moderate to severe, free hemoglobin passes the glomerular filter and appears in the urine. Most of the free hemoglobin in plasma is probably excreted in urine as a dimer with a molecular weight of approximately 32,000. Since true hemoglobinuria results from intravascular hemolysis, the condition is usually accompanied by other clinical problems such as pale mucous membranes, rapid respiratory rate, rapid heart rate, and, in some cases, cyanosis. The presence of true hemoglobinuria necessitates an immediate search for the presence and cause of intravascular hemolysis. Causes of hemolytic anemia are listed in Table 33-2. Hemoglobinuria results from hemolytic anemia only when red cells are destroyed within the vascular system at a rate that exceeds the capacity for conversion of hemoglobin to bilirubin. Therefore, many patients with hemolytic anemia will not have hemoglobinuria but predictively have bilirubinuria and icterus.

TABLE 33-2. Causes and differential diagnosis of hematuria

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