Hematuria and Pigmenturia

Hematuria is defined as blood in the urine. It may appear as occult blood detected during urinalysis, as uniformly red-colored urine throughout urination, or as blood clots passed at any phase of urination.

When clots of blood are visible in the urine, the presence of hematuria is confirmed. Also, when scattered spots of color change are evident on the blood reagent pad of the urine dipstick, the reaction pattern reflects the presence of small aggregates of red cells deposited on the pad. Otherwise, differentiation of hematuria from hemoglobinuria and myoglobinuria requires that the discolored urine be centrifuged and the sediment examined. Hematuria is characterized by red-, pink-, or brown-colored urine that clears partially or entirely after centrifugation, result­ing in a pigmented sediment pellet. With hematuria, red cells or red cell “ghosts” (red cells devoid of pigment) are visible on microscopic examination of urine sediment.

Urine containing hemoglobin is clear to dark red in color, depending on the concentration of hemoglobin in the sample. If visibly discolored, the urine sample with hemoglobinuria does not clear when centrifuged.

Urine containing myoglobin may be of normal color; if present in high concentrations in a sample, it imparts a dark red to brown color to the urine (see Fig. 10.2). If visibly discolored, urine containing myoglobin does not clear when centrifuged. Sediment findings are variable but can include hyaline or cellular casts if pigment nephropathy is present. Myoglobin can be differentiated from hemoglobin in urine through ammonium sulfate precipitation, electrophoresis, or spectroscopy. Animals with myoglobinuria have muscle necrosis or injury, which leads to release of myoglobin from damaged muscle cells into the plasma and renal tubular fluid. Extensive muscle trauma (e.g., dog attacks, trailer accidents) or primary myopathies can induce myoglobinuria. Affected animals may show abnormal stance, gait, or other evidence of muscle swelling, pain, or weakness. The serum activity of the enzymes creatine phosphokinase (CPK), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) is variably increased, depending on the duration and severity of muscle injury. As for hemoglobin, the persistence of myoglobin in the tubular fluid of the nephrons is nephrotoxic and can induce renal tubular necrosis.

Approach to Diagnosis of Hematuria and Pigmenturia

The history should include data on recent infectious diseases, exercise, diet, and treatment, and a full physical examination should be conducted. Hematuria after exercise may indicate the presence of erosions in the urinary tract mucosa, anomalous vascular structures, or mucosal trauma from uroliths. Ingestion of certain toxins (e.g., cantharidin, bracken fern) can create hematuria. Geldings and stallions may develop spontaneous hematuria associated with a vascular fistula or cavernosal rupture in the most proximal urethra.^9-11 Hemoglobinuria can result from exposure to hemolytic toxins such as red maple leaves, copper, onions, and certain bacterial hemolysins. Intravenous infusion of markedly hypotonic (e.g., water) or hypertonic (e.g., undiluted dimethyl sulfoxide [DMSO]) fluids can also result in intravascular hemolysis and hemoglobinuria. In dehydrated animals, ingestion of large volumes of water (water intoxication) can reduce intravascular osmolality to the point of causing hemolysis, with resultant hemoglobinuria.

Hemolysis should be investigated through examination of the serum or plasma, serum total protein measurement, and/ or a complete blood count (CBC). A urine sample should be obtained for full urinalysis, centrifugation, and sediment examination. The patient with potential hematuria should be carefully examined for clinical signs suggestive of impaired coagulation. Severe vulvitis often develops in females with diarrhea because of prolonged contact of the vulvar mucosa with fecal contents, and a trace reaction for blood is often evident in the urine. However, the possibility of hemorrhage

■ BOX 10.2

Causes of Hematuria and Pigmenturia in Horses and Ruminants

Hematuria

Aberrant parasite migration within the urinary tract Admixture of fecal blood with urine

Admixture of blood from the reproductive organs with urine (e.g., metritis, orchitis, seminal vesiculitis)

Arsenic toxicosis

Bleeding diatheses (e.g., warfarin, disseminated intravascular coagulation [DIC])

Cantharidin (blister beetle) poisoning (E)

Cobalt toxicosis (E)

Contamination of urine with oxidant disinfectants

Enzootic hematuria (R)

Exercise-induced hematuria (E)

Habronemiasis (E)

Leptospirosis

Neoplasia of the urogenital tract

Penile, vaginal, preputial, or urethral trauma

Penile masses or encircling hair rings

Renal papillary necrosis (e.g., related to nonsteroidal antiinflam­matory drugs [NSAIDs])

Ulcerative cystitis

Urinary calculi (urolithiasis)

Urinary tract infection

Vascular anomaly, corpus cavernosum rupture (proximal dorsal urethral hemorrhage in males) (E)

Hemoglobinuria

Burns (severe)

Clostridium haemolyticum infection (redwater) (R)

Copper intoxication

Ethylene glycol toxicosis (severe)

Excess water intake, water intoxication

Hepatic failure

Intravenous (IV) hypotonic fluid administration (e.g., 0.45% saline or water)

IV hypertonic fluid administration (e.g., dimethyl sulfoxide [DMSO])

Leptospirosis

Onion and Brassica species (rapeseed, kale, mustard, etc.) intoxication

Neonatal isoerythrolysis

Postparturient hemoglobinuria (combined phosphorus/selenium and/or copper deficiency) (R)

Red maple intoxication (E)

Myoglobinuria

Clostridial myonecrosis Compartment syndrome, down cow syndrome

Exertional or capture rhabdomyolysis

Hereditary or congenital myopathies

Infarctive purpura hemorrhagica (E)

Muscle trauma

Myopathy associated with streptococcal infections (E) Nutritional myodegeneration

Postanesthetic myoneuropathy

Toxic myopathies (e.g., Acer species, Cassia species, ionophores, gossypol)

Viral myopathies (influenza, equine herpesvirus [EHV], bluetongue)

E, Found only in horses; R, found only in ruminants.

from tubular injury caused by hypovolemia should also be considered.

Lesions of the urethra most often produce hematuria at the beginning of urination. Hematuria that originates from the bladder is most likely to be seen or appear more pronounced at the end of urination. Hemorrhage originating from the upper urinary tract is likely to be more pronounced at the end of urination. It should be noted, however, that it is not always possible to accurately localize the source of urinary tract hemor­rhage by the timing of the appearance of blood in the voided sample. If the urine discoloration appears uniform throughout urination and no clots are obvious, it must be determined that the discoloration is hematuria and not hemoglobinuria, bilirubinuria, or myoglobinuria. This can be accomplished by routine dipstick urinalysis; urine sediment examination; assessment of the patient's PCV plasma protein concentration, and serum muscle enzyme activities; and visualization of the color of the plasma and mucous membranes.

Hematuria often accompanies pyuria and bacteriuria UTI. If hematuria is confirmed and UTI or genital or perineal trauma is not the cause, rectal examination may reveal calculi or tumors in the proximal urethra or bladder. Endoscopic examination of the urethra and bladder is necessary if the lesion cannot be detected during rectal or physical examination. During endo­scopic examination of the urethra and bladder, if the source of hemorrhage is not apparent, the openings of the ureters and the color of the urine coming from both of them should be visualized. This is best performed after suctioning urine from the bladder and then distending the bladder with air, taking care that bubbling of the urine does not occur. The two openings can be visualized simultaneously by passing the scope farther into the bladder and retroflexing the scope caudally until the entire trigone area is visualized. If hemorrhage is seen to originate from one or both ureteral openings, ultrasound examination of the kidneys and ureters should be performed, as the hemorrhage has now been localized to the upper urinary tract (UUT).

When myoglobinuria is present, the potential for exposure to gossypol and ionophores should be investigated. Certain viral and bacterial infections, such as streptococcal infections in horses, can induce myopathy and myoglobinuria. A recent history of heavy exertion or very high ambient temperature (heatstroke) may exist in cases of myopathy with myoglobinuria. The potential for nutritional myodegeneration from vitamin E and/or selenium deficiency should be considered in light of the animal's diet and the regional soil selenium content. A previous history of recurrent exercise intolerance or muscle dysfunction may be evident in certain inherited, idiopathic, or diet-associated cases of rhabdomyolysis. Prolonged recumbency (e.g., general anesthesia, downer animals) can induce sufficient pressure myopathy to cause myoglobinuria. Rarely, idiosyncratic responses to medications can induce hemolysis or muscle injury, resulting in hemoglobinuria and myoglobinuria, respectively.