Red urine: Disorders you may have never considered (Proceedings)


Red urine: Disorders you may have never considered (Proceedings)

Apr 01, 2010


Hematuria can be a presenting complaint for a variety of disorders of the urinary tract. The problems causing hematuria can range from relatively minor disorders to more severe disease processes that may result in life-threatening hemorrhage. Urolithiasis, urinary tract infection, drug toxicity, and neoplasia are some of the more common causes of hematuria. For this presentation, three less commonly recognized causes of hematuria are described: i) exercise-associated hematuria, ii) proximal urethral tears in stock type horses, and iii) idiopathic renal hematuria. Before these specific conditions are discussed, a brief overview of hematuria is warranted.

Normal urine contains about 5000 (range 2000 to 10,000) red blood cells (RBCs) per ml. This range of RBC excretion should yield negative results on reagent strip analysis and a report of not more than 5 RBCs per high-power field (hpf) on sediment examination. Increases in RBC excretion may lead to microscopic or macroscopic hematuria. Microscopic hematuria, which implies an increase in RBC excretion that cannot be seen grossly, is usually associated with increases in the range of 10,000 to 2,500,000 RBC per ml. On sediment examination at least 10 RBC/hpf should be apparent. Reagent strip analysis results can range from trace to +++. It is important to recognize that reagent strip results, that utilize the peroxidase-like activity of hemoglobin and myoglobin to oxidize a chromogen in the test pad, do not differentiate between hemoglobin and myoglobin. Thus, positive results are not specific for hematuria and may be more appropriately termed "pigmenturia." Despite this limitation, reagent strips can be used to differentiate hematuria from hemoglobinuria or myoglobinuria when the color change is limited to scattered spots on the test pad. This pattern implies that intact RBCs were adsorbed onto the pad, underwent lysis, and produced a localized color change due to hemoglobin activity on the chromogenic substrates. Ability to differentiate hematuria from excretion of the heme pigments is limited to a threshold of 250,000 to 300,000 RBCs per ml, unless urine samples are diluted with normal saline.

Macroscopic or gross hematuria indicates RBC excretion in excess of 2,500,000 to 5,000,000 RBC per milliliter (or about 0.5 mL blood per liter of urine). Macroscopic hematuria can be differentiated from other causes of pigmenturia by centrifuging a sample of urine to produce a red cell pellet and yellow supernatant urine. In concentrated urine (specific gravity over 1.020), RBCs tend to become crenated, owing to osmotic shift of water out of the cells. In urine with a specific gravity below 1.010, osmotic swelling and dilution of hemoglobin lead to "ghost cell" formation. Further, many RBCs will lyse in dilute urine (especially alkaline urine) so that RBC excretion may be underestimated. Reagent strip analysis can be useful in dilute urine samples to detect hemoglobin released from lysed erythrocytes.

Figure 1. Bladder mucosal erosions in a Standardbred mare with gross hematuria following exercise attributed to "bruising" of the mucosa in a "contrecoup" fashion due to trauma of the bladder against the pelvic brim during exercise.
Noting the timing of hematuria can be a practical means of initially localizing the site of urinary tract hemorrhage. Hematuria throughout urination is consistent with hemorrhage from the kidneys, ureters, or bladder, whereas hematuria at the beginning of urination is often associated with lesions in the distal urethra. Hematuria at the end of urination is usually the result of hemorrhage from the proximal urethra or bladder neck. A thorough diagnostic evaluation, including physical examination, rectal palpation, analyses of blood and urine, endoscopy of the lower tract, and ultrasonography, is usually rewarding in establishing the source and cause of urinary tract hemorrhage.

Exercise-associated hematuria

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Exercise is accompanied by increased filtration of RBCs and protein across the glomerular barrier in a high percentage of human and equine athletes. Typically, hematuria is microscopic but occasionally gross discoloration of urine may be observed. Gross hematuria may more commonly be a consequence of bladder mucosal erosions that may be traumatically induced by the abdominal contents pounding the bladder against the pelvis during exercise. Detection of focal bladder erosions or ulcers with a contrecoup distribution and a history of emptying the bladder immediately prior to the exercise bout would be characteristic for this problem (Figure 1). A diagnosis of exercise-associated hematuria should be one of exclusion after diagnostic evaluation has ruled out more common causes of hematuria such as presence of a cystolith.