Red means stop

In the Dr. Seuss classic Go Dogs Go, we learn a very important lesson that remains with us throughout our lives: Red means stop.

It is a very simple concept, and surprisingly is just as applicable to real horses performing in athletic competition as it is to storybook dogs racing cars around the unusual landscapes of Dr. Seuss's books.

Photo 1: Urine from a heavily muscled horse that developed exertional rhabdomyolysis at an endurance ride. The deep red color is being produced by myosin pigment cleared through the kidney and into the urine. This horse required intravenous fluid therapy for recovery. Less serious hematuria might also look like this, but the clinical signs would be helpful in determining the correct diagnosis.

Red means stop, and the presence of red-colored urine in an equine athlete generally is a cause for concern. Bloody or discolored urine actually is one of the most common findings among equine and human athletes. This condition is called exercise-induced hematuria; according to Dr. Robert Gambrell, a sports medicine physician in Augusta, Ga., "although most cases of discolored urine following strenuous exercise are mild and not associated with serious disease, hematuria in the athlete must still be differentiated from other potentially more serious conditions."

Dr. Martha Terris, assistant professor of urology at the Stanford School of Medicine, goes even further, warning, "Pink or red urine should prompt an immediate visit to your doctor."

Incidence in humans and horses

The incidence of exercise-induced hematuria in humans is between 11 percent and 100 percent, depending on the type and amount of exercise and the athlete's state of hydration. It has been known as sports hematuria, runner's hematuria or 10,000-meter hematuria, and was first reported in humans in 1700.

Photo 2: This is a series of urine samples (earliest on the left and most recent at right) from another horse that tied up at an endurance event. This horse has been on intravenous fluids and the samples show the value of "flushing" the dangerous myoglobin molecules from the kidneys. These horses are considered at risk until the urine again appears clear and light yellow.

The number of sports and activities associated with discolored urine in humans is very large and includes everything from traditional football, hockey and boxing to swimming, track, lacrosse, soccer and even snowmobiling, bike riding and rowing.

The incidence of exercise-induced hematuria in horses is much harder to determine because the actual discolored urine often is not observed, depending on the nature and duration of the particular equine sport.

Abnormal color of a normal bodily fluid is understandably much more noticed and reported in humans. Research studies done in horses, however, do show a very high correlation with the incidence of exercise-induced hematuria seen in human athletes. Drs. Hal Schott, David R. Hodgson and Warwick Bayly of the Department of Clinical Sciences, College of Veterinary Medicine at Washington State University, reported that grossly discolored urine was noted in 100 percent of horses exercising on a treadmill at speeds using both 60 percent and 95 percent of the maximal oxygen consumption (V02max).

Photo 3: Strenuous exercise is associated with hematuria in equine athletes and its severity is associated with the type of activity, speed involved, length of time competing and the hydration status of the horse. Attention to all of these factors will help reduce or eliminate hematuria in these horses.

Seven out of eight horses exercising at only 40 percent V02max still showed hematuria if the urine sample was centrifuged and examined via reagent strip analysis to detect the presence of red blood cells. These researchers concluded that exercise-induced hematuria (along with significant proteinuria) is very common in equine athletes as well, even if gross hematuria is not observed.

Exercise-induced hematuria is classified either as gross (visible in the urine by eye) or microscopic (clear urine but presence of red blood cells noted on testing). Microscopic hematuria is by far the more common, again leading to probable under-recognition in equine athletes. The cause of sports hematuria is not well understood, however, and might possibly be different depending on the type and duration of exercise.

The colors: what they mean

Five causes

Five general causes have been proposed that address the variations in sporting activities and anatomical location for red blood cell loss.

1. Traumatic renal hematuria is thought to occur from damage to the renal vasculature. This may be from a direct blow and contact (hockey, boxing and football in humans and polo or rodeo sports in horses), or from indirect trauma from shaking and jostling (all types of racing, endurance, jumping, reigning, cutting, driving).

2. Non-traumatic renal injury is thought to occur because of hypoxic renal nephron damage due to reduced kidney blood flow. "During exercise, blood is preferentially shifted to the skeletal muscles, heart and lungs," explains Gambrell. This shifting of blood volume results in a decreased renal blood flow, which is in proportion to the intensity and duration of exercise and affected by the hydration status of the athlete. Studies have shown that swimmers and runners in shorter events have much less hematuria than those athletes competing in longer distance events. "Decreased renal blood flow results in hypoxic damage to the nephron, which increases glomerular permeability," according to Gambrell, "which theoretically allows excretion of red blood cells into the urine, along with significant protein leakage."

3. Another possible cause of exercise-induced hematuria is trauma to the lining of the bladder. As the human or equine runner moves, the bladder is constantly flapping forward and back, and bruising can occur. The anatomy of the horse is somewhat different, making horses more capable of running with reduced bladder trauma over the short distances required to elude predators. The horse, however, was not designed to run for the distances required with endurance sports or to repetitively jump large obstacles. These sports-related movements likely stress the bladder lining, causing bruising and leading to hematuria (also known as "bongo-drum hematuria").

Hematuria has been reported due to prostatic (not found in the horse) or urethral origin in humans, but these causes are not believed to be a significant factor in horses.

Fortunately, most cases of exercise-induced hematuria resolve within days of cessation of exercise and do not develop into more severe conditions.

4. Bladder infections, kidney and bladder stones, various cancers and other serious conditions can cause red urine, so persistent cases of red urine must be treated seriously and those horses should be subjected to a complete diagnostic work-up, including blood work, urine analysis, cystoscopy and radiographs.

Recommendations for reducing the incidence and severity of exercise-induced hematuria include maximal hydration before exercise to ensure a full bladder, which helps reduce bladder-wall trauma and keep renal blood flow as nearly normal as possible. Better fitness and conditioning can reduce the severity of hematuria because an efficient cardiovascular system and non-fatigued muscles require less blood flow, protecting kidney function.

5. The other significant cause of urine discoloration in the performance horse is myoglobin which is the major portion of the muscle sarcoplasm and functions as an oxygen storage molecule. Horses experiencing muscle damage from sprains, strains and tears all the way to complete metabolic muscle dysfunction in a case of exertional rhabdomyolysis (tying up) will show varying degrees of myoglobinuria, because this pigment is released from damaged muscles and cleared through the kidneys into the urine.

Tying-up horses typically show a reluctance to move along, with hard, swollen muscles of the back, rump, hips and upper rear legs. The urine from horses with exertional rhabdomyolysis is dark brown to red to coffee-colored. Discolored urine of this nature, along with the typical clinical signs of tying up, always should be treated seriously. Myoglobin is damaging to the kidneys and often untreated exertional rhabdomyolysis cases develop kidney failure. Fluid therapy is crucial in these cases, along with appropriate pain relief, anti-inflammatory, vasoactive drugs and supportive care.

Tough call for practitioners

Veterinarians working horse shows, three-day events, endurance rides and other equine competitions often are placed in a difficult position when presented with a horse with red urine. A horse experiencing simple exercise–induced hematuria is not in distress and could realistically continue to compete without risk.

Research would suggest that the vast majority of equine athletes already routinely experience some degree of exercise-induced hematuria, whether owners, trainers, riders or veterinarians actually observe or document it.

A horse exhibiting red urine due to myoglobinuria, however, is in danger, and should be removed from competition and treated aggressively. Muscle enzymes, urinalysis and clinical examination should help the clinician differentiate between these two conditions.

Free hemoglobin produces a pink serum, which will be positive for red blood cells when tested with a strip assay. "Myoglobin is cleared more efficiently by the kidneys, leaving a clear serum which will test negatively," says Terris.

When in doubt, it is better in these situations to err on the side of caution. Clinicians need only remember those lessons learned early on: Red means stop.