Hematuria is defined as the presence of blood or red blood cells in the urine. An anatomical framework is helpful in developing a comprehensive differential diagnosis. Blood or red blood cells can enter and mix with urine at multiple anatomical sites. These include the urinary system, female reproductive system, and integumentary system. Urinary causes occur anywhere between the kidney glomerulus and the urethral meatus. These can be divided into glomerular and non-glomerular causes. Non-glomerular causes can be further subdivided into upper urinary tract and lower urinary tract causes. After conducting a thorough history and physical examination, further medical testing is warranted. Patients can be stratified into high and low risk. High-risk patients include those with visible hematuria or those with non-visible hematuria and risk factors. A complete evaluation of the urinary tract is indicated for hematuria. This includes imaging of the upper urinary tract and cystoscopy of the lower urinary tract.
Differential diagnosis
Urinary causes occur anywhere between the kidney glomerulus and the urethral meatus. These can be divided into glomerular and non-glomerular causes. Non-glomerular causes can be further subdivided into upper urinary tract and lower urinary tract causes. In general, nephrologists are the experts of glomerular hematuria while urologists manage non-glomerular hematuria. The differential diagnosis can be furthered refined by the temporality of hematuria and associated symptoms. Microscopic hematuria has a prevalence of 2% to 31%, depending upon age, sex, and other factors.
Glomerular hematuria
A glomerular etiology is suggested by dysmorphic red blood cells, protein, and cellular casts in the urine. This requires the consultation of a nephrologist. Common causes include:
requires medical testing for detection. It is not visible to the naked eye. Rather it requires microscopic examination for detection. It is defined as three or more red blood cells per high-powered field. Another method for detection of microscopic hematuria is the dipstick method. This test works by detecting hemoglobin in a urine sample. False positives can occur with dipstick testing if free hemoglobin or myoglobin are present. "Red urine" can result from the drug phenazopyridine.
Hemoglobinuria
in the absence of red blood cells can also turn urine red. The inciting event for hemoglobin in the urine is hemolysis in the bloodstream. Hemolysis is a process where red blood cells lyse or burst. This releases hemoglobin into the bloodstream. Hemoglobin then leaves the bloodstream and enters urinary tract at Bowman's capsule.
After conducting a thorough history and physical examination, further medical testing is warranted. Patients can be stratified into high and low risk. High-risk patients include those with visible hematuria or those with non-visible hematuria and risk factors. A complete evaluation of the urinary tract is indicated for hematuria. This includes imaging of the upper urinary tract and cystoscopy of the lower urinary tract.
Associated symptoms
The differential diagnosis can be furthered refined by the temporality of hematuria and associated symptoms. During urination, blood can appear in the urine at the onset, midstream, or later. It can also have associated symptoms. These include nausea, fever, chills, abdominal pain, flank pain, groin pain, urinary frequency, urinary urgency, and pain or discomfort with urination. When hematuria becomes visible during urination can suggest where in the urinary tract the bleeding originates. If it appears soon after the onset of urination, a distal site is suggested. A longer delay suggests a more proximal lesion. In other words, shorter times suggest distal sites while longer times suggest proximal sites. Hematuria that occurs throughout urination suggests that bleeding is occurring above the level of the bladder. The presence of hematuria without accompanying symptoms should be considered a tumor of the urinary tract until proven otherwise. Other possible causes include acute glomerulonephritis, staghorn calculus, polycystic kidneys, benign prostatic hyperplasia, solitary renal cyst, sickle cell disease, and hydronephrosis. It can also develop after vigorous exercise. Costovertebral angle tenderness suggests upper urinary tract obstruction. A urinary stone is suggested by the presence of renal colic. The presence of a fever suggests pyelonephritis.
Upper urinary tract imaging
The preferred modality is a multi-phasic computed topography urography. This is a three-phase study that includes a non-contrast phase, an arterial phase, and an excretory phase. The study should sufficiently evaluate the kidney and the urothelium lining the upper urinary tracts. If there are contraindications to this study then alternative studies can be used. One alternative is a magnetic resonance urography with and without intravenous contrast. Another alternative is a retrograde pyelogram paired with either magnetic resonance imaging of the upper urinary tracts or a renal ultrasound. This imaging assessment is capable of excluding upper tract malignancies.
Younger people
For patients younger than 35 years old presenting with asymptomatic microscopic hematuria, a cystoscopy may be warranted if risk factors are present.
Initial negative evaluation
Evaluations of hematuria that do not reveal pathology require follow up. A urinary cytology may be helpful. A urinalysis should be repeated once a year. Follow up can be discontinued after two consecutive negative urinalyses. Repeat hematuria on follow-up studies warrants repeat upper urinary tract imaging and a cystoscopy. This should be performed within three to five years of the first evaluation.
Management
Acute clot retention
Acute clot retention is one of three emergencies that can occur with hematuria. The other two are anemia and shock. Blood clots can prevent urine outflow through either ureter or the bladder. This is known as acute urinary retention. Blood clots that remain in the bladder are digested by urinary urokinase producing fibrin fragments. These fibrin fragments are natural anticoagulants and promote ongoing bleeding from the urinary tract. Removing all blood clots prevents the formation of this natural anticoagulant. This in turns facilitates the cessation of bleeding from the urinary tract. The acute management of obstructing clots is the placement of a large urethral Foley catheter. Clots are evacuated with a Toomey syringe and saline irrigation. If this does not control the bleeding, management should escalate to continuous bladder irrigation via a three-port urethral catheter. If both a large urethral Foley catheter and CBI fail, an urgent cystoscopy in the operating room will be necessary. Lastly, a transfusion and/or a correction of a coexisting coagulopathy may be necessary.
Epidemiology
In the United States of America, microscopic hematuria has a prevalence of somewhere between 2% and 31%. Higher rates exist in individuals older than 60 years of age and those with a current or past history of smoking. Only a fraction of individuals with microhematuria are diagnosed with a urologic cancer. When asymptomatic populations are screened with dipstick and/or microscopy medical testing about 2% to 3% of those with hematuria have a urologic malignancy. Routine screening is not recommended. Individuals with risk factors who undergo repeated testing have higher rates of urologic malignancies. These risks factors include age, male gender, previous or current smoking, chemical exposure, and prior pelvic radiation therapy.
Children
In pediatric populations, the prevalence is 0.5–2%. Risks factor include older age and female gender. About 5% of individuals with microscopic hematuria receive a cancer diagnosis. 40% of individuals with macroscopic hematuria receive a cancer diagnosis.
