Hematuria (erythrocyturia)

 

Classification and Causes of Hematuria

Hematuria can be classified based on the presumed origin of the bleeding along the urinary system or due to systemic factors:

 

Prerenal Hematuria

Prerenal hematuria occurs, as a rule, in diseases accompanied by a hemorrhagic syndrome. This type of hematuria is typically due to impaired permeability of the capillary walls throughout the body or defects in the hemostatic system (coagulation disorders). It is more often observed in the form of microscopic hematuria. Examples include:

• Coagulopathies (e.g., hemophilia, von Willebrand disease, liver disease causing deficient clotting factor synthesis, disseminated intravascular coagulation - DIC).
• Thrombocytopenia (low platelet count) or platelet dysfunction.
• Anticoagulant or antiplatelet medication use.
• Severe systemic infections (sepsis) leading to increased capillary permeability or DIC.
• Vasculitides affecting small vessels systemically.

 

Renal Hematuria (Glomerular and Non-Glomerular)

Renal hematuria originates from the kidneys themselves. It can be further divided into glomerular (arising from the glomeruli) and non-glomerular (arising from tubules, interstitium, or renal vasculature).

• Glomerular Hematuria: Caused by damage to the glomerular filtration barrier, allowing red blood cells to pass into Bowman's space and the renal tubules. Evidence of glomerular hematuria includes the presence of dysmorphic red blood cells (especially acanthocytes) and erythrocyte casts in the urine sediment. Diseases causing significant glomerular hematuria include:
  • Acute or chronic glomerulonephritis (e.g., IgA nephropathy, post-infectious glomerulonephritis, lupus nephritis, membranoproliferative glomerulonephritis). Hematuria in some acute nephritis complicating infectious diseases (like scarlet fever, influenza, rubella, tonsillitis) often presents as microhematuria.
  • Nephrosclerosis (damage due to hypertension or arteriosclerosis).
  • Thin basement membrane disease.
  • Alport syndrome.
• Non-Glomerular Renal Hematuria:
  • Kidney stones (nephrolithiasis) causing trauma to the renal pelvis or calyces.
  • Kidney cancer (e.g., renal cell carcinoma, transitional cell carcinoma of the renal pelvis).
  • Renal infarction due to embolism or thrombosis.
  • Kidney tuberculosis.
  • Polycystic kidney disease.
  • Pyelonephritis (severe kidney infection can sometimes cause hematuria).
  • Papillary necrosis (e.g., due to diabetes, analgesic abuse, sickle cell disease).
  • Renal trauma.
  • Interstitial nephritis.

 

Postrenal Hematuria

Postrenal hematuria is caused by bleeding originating from the urinary tract structures distal to the kidneys: the ureters, bladder, prostate (in males), or urethra. The erythrocytes are typically isomorphic (unchanged).

The most common causes of postrenal hematuria include:

• Cystitis (Bladder Inflammation/Infection): Especially hemorrhagic cystitis.
• Urethritis (Urethral Inflammation/Infection).
• Urinary Tract Stones: Ureteral stones or bladder stones causing mucosal trauma.
• Tumors: Bladder cancer (transitional cell carcinoma), ureteral tumors, prostate cancer, or urethral cancer.
• Prostate Conditions: Benign prostatic hyperplasia (BPH) can cause bleeding. Prostatitis.
• Trauma: Injury to the bladder, urethra, or ureters.
• Urethral strictures or foreign bodies.
• Radiation cystitis or urethritis.
• Rupture of a vessel in the prostate.

 

Diagnostic Approach to Hematuria

Initial Evaluation and Urinalysis

The initial step involves confirming true hematuria (presence of RBCs) and distinguishing it from pseudohematuria (red urine due to pigments like hemoglobin, myoglobin, beets, or medications like rifampin). A detailed medical history and physical examination are performed, followed by urinalysis with microscopy.

 

Localization of Bleeding (Two- and Three-Glass Test)

For topical diagnosis of erythrocyturia in urological practice, particularly to differentiate urethral bleeding from bladder or upper tract bleeding, a **two-glass test** or **three-glass test** can be used. The patient urinates sequentially into two or three separate containers.

Interpretation of sample results:

• Initial Hematuria: Predominance of erythrocytes in the first portion of urine (and often discharge of blood before or at the start of urination) typically indicates bleeding from the anterior urethra.
• Terminal Hematuria: Predominance of erythrocytes in the third (final) portion of urine is characteristic of a lesion in the bladder neck or prostate. Sometimes blood appears only in the last drops of urine.
• Total Hematuria: An even distribution of red blood cells in all three portions (or throughout urination in a single sample) suggests bleeding from the bladder or upper urinary tract (ureters, kidneys). The presence of erythrocyte casts specifically confirms a renal (glomerular or tubular) origin of erythrocytes.
• Predominance of erythrocytes in the first and third portions of urine may suggest damage to the prostatic part of the urethra.

This test is less commonly used now with advanced imaging but can still provide useful initial clues.

 

Further Investigations

Depending on the clinical suspicion, further investigations may include:

• Blood Tests: Complete blood count (CBC), renal function tests (creatinine, BUN, eGFR), coagulation profile (PT, PTT, INR), electrolytes, PSA (in men).
• Urine Cytology: To screen for malignant cells, especially in older patients or those with risk factors for urothelial cancer.
• Imaging:
  • Ultrasound of Kidneys and Bladder: A common initial imaging modality to look for stones, tumors, hydronephrosis, or gross kidney abnormalities.
  • CT Urography (CT IVP): Provides detailed images of the kidneys, ureters, and bladder. Excellent for detecting stones, tumors, and structural abnormalities. Often the preferred imaging for evaluating hematuria.
  • MRI Urography: May be used if CT is contraindicated (e.g., contrast allergy, pregnancy) or for better soft tissue delineation.
  • Cystoscopy: Direct visualization of the urethra and bladder lining using a cystoscope. Essential for evaluating bladder lesions, tumors, stones, or sources of bleeding within the bladder. Biopsies can be taken.
  • Ureteroscopy/Nephroscopy: Endoscopic examination of the ureters and renal pelvicalyceal system if an upper tract source is suspected and not identified by other means.
• Kidney Biopsy: If glomerular disease is suspected based on dysmorphic RBCs, RBC casts, significant proteinuria, or declining renal function.

 

Differential Diagnosis of Hematuria by Origin

Origin of Hematuria	Common Causes	Typical Urine Findings
Glomerular (Kidney - Nephrological)	Glomerulonephritis (IgA nephropathy, lupus nephritis, post-infectious GN, thin basement membrane disease, Alport syndrome), diabetic nephropathy.	Dysmorphic RBCs (especially acanthocytes), RBC casts, often associated with proteinuria.
Non-Glomerular Renal (Kidney - Urological/Medical)	Kidney stones, renal cell carcinoma, transitional cell carcinoma of renal pelvis/ureter, polycystic kidney disease, pyelonephritis, renal infarction, papillary necrosis, renal trauma, interstitial nephritis.	Isomorphic (eumorphic) RBCs, no RBC casts (unless concomitant glomerular issue). WBCs/WBC casts if pyelonephritis.
Postrenal - Ureteral	Ureteral stones, ureteral tumors (TCC).	Isomorphic RBCs. May have ureteral colic.
Postrenal - Bladder	Bladder stones, bladder tumors (TCC), cystitis (bacterial, hemorrhagic, radiation, interstitial), trauma.	Isomorphic RBCs. Symptoms of bladder irritation (frequency, urgency, dysuria) common with cystitis.
Postrenal - Prostate (Males)	Benign prostatic hyperplasia (BPH), prostate cancer, prostatitis.	Isomorphic RBCs. Often associated with lower urinary tract symptoms (LUTS).
Postrenal - Urethral	Urethritis, urethral stricture, urethral tumors, trauma (e.g., catheterization), urethral stones.	Isomorphic RBCs. Often initial hematuria. Dysuria, urethral discharge may be present.
Prerenal/Systemic	Coagulation disorders, anticoagulant therapy, severe hypertension, strenuous exercise, sickle cell disease/trait, systemic infections (sepsis).	Isomorphic RBCs (unless concomitant renal damage). Evidence of systemic disease or medication use.

 

Management of Hematuria

The management of hematuria is entirely dependent on identifying and treating the underlying cause. There is no specific treatment for hematuria itself, as it is a symptom.

• Observation: For benign causes like exercise-induced hematuria or transient causes, observation may be sufficient.
• Medical Treatment: For infections (antibiotics), glomerulonephritis (immunosuppression, blood pressure control), or systemic diseases.
• Surgical/Procedural Treatment: For tumors (resection, chemotherapy, radiation), large stones (lithotripsy, ureteroscopy, percutaneous nephrolithotomy), BPH (medications or surgery like TURP), or structural abnormalities.
• Lifestyle Modifications: E.g., increased fluid intake for stone prevention, dietary changes for certain kidney conditions.

If hematuria is severe and causing significant blood loss, supportive measures like fluid resuscitation or blood transfusion may be necessary while the cause is being investigated and treated.

 

When to Consult a Physician or Urologist/Nephrologist

Any instance of visible blood in the urine (gross hematuria) warrants prompt medical evaluation. Microscopic hematuria detected on routine urinalysis also requires further investigation. Consultation with a primary care physician is the first step, who may then refer to a urologist (for suspected lower tract or non-glomerular renal causes) or a nephrologist (for suspected glomerular causes).

Seek medical attention if you notice:

• Pink, red, brown, or cola-colored urine.
• Blood clots in the urine.
• Hematuria accompanied by pain (flank, abdominal, during urination), fever, or difficulty urinating.
• Recurrent episodes of hematuria.
• Hematuria if you are on blood-thinning medications.
• Risk factors for urinary tract cancer (e.g., age >40, smoking history, occupational chemical exposure) and hematuria.

Early diagnosis and treatment of the underlying cause of hematuria are crucial for preventing potential complications and ensuring the best possible outcome.