Pyuria, leucocyturia (WBC in the urine)

 

Diagnosis and Interpretation of Pyuria

Urinalysis and Microscopy

The primary method for detecting pyuria is urinalysis:

• Dipstick Test: Contains a pad that detects leukocyte esterase, an enzyme released by neutrophils. A positive test suggests the presence of WBCs.
• Microscopic Examination: Centrifuged urine sediment is examined under a microscope to count the number of WBCs per high-power field (HPF). The morphology of WBCs and the presence of other elements (bacteria, red blood cells, casts, crystals, epithelial cells) are also noted.

The simultaneous detection of leukocytes and squamous epithelial cells in a urine sample from a female often suggests contamination from vaginal secretions rather than a true UTI, and a repeat, properly collected midstream clean-catch sample may be needed. The presence of urethral filaments (mucus strands containing WBCs) along with leukocytes in the urine indicates inflammation of the urethra (urethritis).

 

Topical Diagnosis (Two- and Three-Glass Tests)

For localizing the source of leukocyturia (pyuria) within the male urinary tract, particularly in urological practice, a **two-glass test** or a **three-glass test** can be employed. The patient is instructed to urinate sequentially into two or three separate sterile containers:

• Two-Glass Test: The initial portion of urine (e.g., 50-60 ml, representing urethral washings) is collected in the first vessel, and the rest of the voided urine (midstream, representing bladder urine) is collected in the second vessel.
• Three-Glass Test:
  1. **First Portion (VB1 or Initial Void):** First 10-15 mL of urine, representing urethral contents.
  2. **Second Portion (VB2 or Midstream):** Middle part of the urinary stream, representing bladder urine.
  3. **Third Portion (VB3 or Post-Prostatic Massage Urine):** After collecting VB2, the physician performs a prostatic massage, and any expressed prostatic secretions (EPS) along with the first few drops of urine voided immediately after massage are collected in the third vessel. (Alternatively, some protocols collect terminal urine without massage as the third glass, reflecting bladder neck/prostatic urethra contents at the end of voiding).

The degree of turbidity (cloudiness) and color intensity of the urine in each vessel is observed visually, followed by microscopic examination of the urinary sediments from each portion.

 

Interpreting Test Results for Localization (Primarily for Males)

The findings from these multi-glass tests can help pinpoint the site of inflammation:

• Initial Pyuria (Clouding and Leukocytes Primarily in the First Glass): Suggests an inflammatory process in the anterior urethra (urethritis).
• Terminal Pyuria (Opacity and Leukocytes Primarily in the Second Glass of a two-glass test, or Third Glass without massage): Can indicate damage to the bladder neck, posterior urethra, or prostate/seminal vesicles.
• Total Pyuria (Presence of Pus/Leukocytes in All Portions): Suggests an inflammatory process in the bladder (cystitis), or higher up in the urinary tract involving the renal pelvis and kidneys (pyelonephritis).
• Pyuria Predominantly in the Third Glass after Prostatic Massage (Three-Glass Test): This specifically reveals the source of pyuria to be in the prostate gland. In this scenario, pus and inflammatory cells from the prostate enter the urine at the end of the act of urination, particularly with the contraction of the pelvic floor muscles and the emptying of prostatic secretions stimulated by the massage.

The simultaneous detection of **leukocyte casts (WBC casts)** and granular casts in the urine sediment is a strong indicator of a renal origin of the leukocyturia, pointing towards pyelonephritis or interstitial nephritis.

 

Further Investigations

Depending on the clinical context and initial findings, further tests may include:

• Urine Culture and Sensitivity: To identify bacterial pathogens and guide antibiotic choice.
• Blood Tests: CBC, inflammatory markers (ESR, CRP), renal function tests.
• Imaging Studies: Ultrasound, CT scan, or MRI of the urinary tract to look for structural abnormalities, stones, obstruction, abscesses, or tumors.
• Cystoscopy or Ureteroscopy: Endoscopic examination if bladder or upper tract pathology is suspected.
• Tests for Specific Infections: E.g., STI screening (for *N. gonorrhoeae*, *C. trachomatis*, *Trichomonas*), tests for tuberculosis if suspected.

 

Clinical Significance and Associated Symptoms

Pyuria is a significant finding that usually prompts investigation for an underlying cause. Associated symptoms depend on the location and nature of the inflammation/infection:

• Lower UTI (Cystitis/Urethritis): Dysuria (painful urination), urinary frequency, urgency, suprapubic pain, urethral discharge.
• Upper UTI (Pyelonephritis): Flank pain, fever, chills, nausea, vomiting, CVA tenderness, systemic malaise.
• Prostatitis: Perineal pain, pelvic pain, dysuria, ejaculatory pain, fever (in acute).
• Urolithiasis: Renal colic, hematuria.
• Tumors: Hematuria, obstructive symptoms, pain (may be asymptomatic initially).

Sterile pyuria (WBCs in urine without bacteria) is particularly important to investigate further for conditions like interstitial nephritis, genitourinary tuberculosis, or partially treated UTIs.

 

Management Principles for Pyuria

The management of pyuria is entirely directed at treating the underlying cause identified through diagnostic evaluation:

• Bacterial Infections (UTIs, Pyelonephritis, Prostatitis): Appropriate antibiotic therapy based on likely pathogens and culture/sensitivity results.
• Specific Infections: Targeted antimicrobial therapy (e.g., metronidazole for Trichomonas, specific regimens for tuberculosis or gonorrhea).
• Urolithiasis: Pain management, medical expulsive therapy, or procedures to remove/fragment stones (ESWL, ureteroscopy, PCNL).
• Inflammatory Conditions (e.g., Interstitial Nephritis, Interstitial Cystitis): Discontinuation of offending drugs, corticosteroids, or specific therapies for the condition.
• Tumors: Surgical resection, chemotherapy, radiation therapy as indicated.
• Structural Abnormalities: Surgical correction if contributing to infection or obstruction.

Symptomatic relief for pain and fever (analgesics, antipyretics) is also part of management.

 

Differential Diagnosis of Pyuria

Pyuria is a common finding that can be associated with a wide range of conditions. The differential diagnosis focuses on identifying the source and nature of the inflammation:

Category of Cause	Specific Conditions	Associated Findings
Infections of Urinary Tract	Cystitis, Urethritis, Prostatitis, Pyelonephritis, Epididymo-orchitis	Often positive urine culture, dysuria, frequency, urgency, fever, flank/pelvic pain.
Sterile Pyuria - Infectious	Genitourinary Tuberculosis, Chlamydia/Mycoplasma/Ureaplasma urethritis, Viral cystitis, Partially treated UTI, Fungal UTI	Symptoms may mimic bacterial UTI but standard cultures negative. Special cultures/tests needed.
Sterile Pyuria - Non-Infectious Inflammatory	Interstitial Nephritis (drug-induced, autoimmune), Interstitial Cystitis/Bladder Pain Syndrome, Kawasaki Disease, Tubulointerstitial diseases, Glomerulonephritis (some forms)	Symptoms vary by condition. May have hematuria, proteinuria, systemic symptoms. Biopsy sometimes needed.
Urolithiasis (Stones)	Kidney, ureteral, or bladder stones	Can cause inflammation and pyuria even without infection. Hematuria, renal colic common.
Neoplasms	Bladder cancer, Renal cell carcinoma, Prostate cancer, Ureteral/Pelvic tumors	Hematuria often prominent. Pyuria due to inflammation or secondary infection. Diagnosed by imaging/cystoscopy/biopsy.
Trauma/Instrumentation	Recent catheterization, urological procedures, pelvic trauma	Transient pyuria due to mechanical irritation or introduction of bacteria.
Contamination	Vaginal discharge, poor collection technique	Often many squamous epithelial cells in urine. Repeat clean-catch sample needed.

 

When to Consult a Physician or Urologist

Pyuria detected on a urinalysis usually warrants further medical evaluation. Consultation with a primary care physician or a urologist is recommended if:

• Pyuria is newly discovered.
• Symptoms of a urinary tract infection are present (dysuria, frequency, urgency, fever, flank pain).
• Pyuria is persistent or recurrent.
• Sterile pyuria is found (WBCs in urine without bacteria on standard culture).
• There is associated hematuria or significant proteinuria.
• The individual has risk factors for complicated UTIs (e.g., diabetes, immunosuppression, known urinary tract abnormalities).

A thorough investigation will help determine the cause of pyuria and guide appropriate treatment to prevent potential complications like recurrent infections, kidney damage, or spread of infection.