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Epithelial and Leukocyte Cells in Urine Microscopy
Cellular elements in urine sediment come from two sources: (1) desquamated epithelial lining cells of the kidney and lower urinary tract, and (2) cells of hematogenous origin (leukocytes and erythrocytes). Bright-field microscopy works best with a crystal-violet safranin stain to delineate formed elements; phase-contrast microscopy helps with translucent structures.
Leukocytes (White Blood Cells)
Neutrophils (PMNs)
The predominant WBC type in urine.
- Size: ~12 μm in diameter
- Appearance: Granular spheres with multilobated (segmented) nuclei
- Degenerating forms: Nuclear detail is lost; may be confused with renal tubular epithelial cells. Adding dilute acetic acid enhances nuclear detail.
- Glitter cells: In dilute/hypotonic urine, neutrophils swell and their granules show Brownian movement, giving a sparkling refractile appearance.
- Normal: < 5 leukocytes/hpf
- Pyuria: > 5 leukocytes/hpf - indicates infection or inflammation. > 30 cells/hpf suggests acute infection.
- Clinical significance: Pyelonephritis, cystitis, urethritis, prostatitis. Leukocyte casts + pyuria = renal origin.
Staining: With crystal-violet safranin - nuclei appear reddish-purple, cytoplasmic granules violet. Leukocyte esterase strip confirms pyuria in hypotonic specimens.
Fig. 29.6 - Neutrophils with dilute acetic acid (x100):
Eosinophils
- Not normally seen; > 1% of leukocyte population is significant
- Requires Hansel stain (methylene blue + eosin-Y in methanol), Wright, or Papanicolaou stain for identification
- Clinical significance: Allergic interstitial nephritis (drug hypersensitivity - penicillins), UTIs, renal transplant rejection
Lymphocytes and Mononuclear Leukocytes
- Small lymphocytes normally present in small numbers
- Mononuclear cells (histiocytes, lymphocytes, plasma cells) constituting ≥ 30% of differential = chronic inflammation
- Increased lymphocytes in renal transplant rejection
Epithelial Cells
1. Squamous Epithelial Cells
The most common and least significant epithelial cells in urine.
- Origin: Distal one-third of urethra; in females, also from vagina/vulva
- Size: Large (largest epithelial cells in urine)
- Appearance: Flat, abundant cytoplasm, small round central nucleus, edges often folded
- Staining: Nuclei purple, cytoplasm pink to violet (crystal-violet safranin)
- Significance: Contamination marker; large numbers in female urine suggest vaginal contamination
Fig. 29.8 - Squamous epithelial cell, Pyridium stained (x200):
2. Transitional (Urothelial) Epithelial Cells
- Origin: Renal pelvis to lower third of urethra
- Size: 40-200 μm; smaller than squamous cells
- Appearance: Round or pear-shaped, round centrally located nucleus; occasional binucleate forms; characteristic endo-ecto cytoplasmic rim
- Staining: Dark-blue nuclei, pale-blue cytoplasm
- Significance: A few are normal (desquamation). Large clumps or sheets without instrumentation - requires cytology to rule out transitional cell carcinoma
Fig. 29.9 - Transitional epithelial cells, Papanicolaou stained (x430):
(Arrows point to characteristic pear-shaped cells with prominent nuclei)
3. Renal Tubular Epithelial Cells (RTECs)
The most clinically significant epithelial cells - increased numbers indicate tubular damage.
Proximal/Distal Convoluted Tubular Cells:
- Size: 14-60 μm (large, oblong)
- Coarsely granular eosinophilic cytoplasm
- Small nuclei with dense chromatin, rare nucleoli; may be multiple
Collecting Duct Cells:
- Size: 12-20 μm
- Cuboidal or polygonal shape
- Large, slightly eccentric nucleus
- Basophilic endo-ecto cytoplasmic rim
Clinical significance of RTECs:
| Condition | Finding |
|---|
| Acute tubular necrosis (ATN) | Increased RTECs + granular casts + "muddy brown" casts |
| Drug/heavy metal toxicity | Increased proximal/distal tubular cells |
| Renal transplant rejection | Collecting duct cells + eosinophils + lymphocytes |
| Ischemic necrosis | Renal epithelial fragments (≥3 collecting duct cells = basement membrane disruption) |
Fig. 29.10 - Renal tubular epithelial cells (x200):
Fig. 29.11 - Renal tubular epithelial cells and neutrophils, Papanicolaou stained:
(Larger epithelial cells with prominent nuclei alongside smaller neutrophils)
Quick Comparison Table
| Cell Type | Size | Key Feature | Normal Limit | Significance |
|---|
| Neutrophil | ~12 μm | Multilobed nucleus, granular | < 5/hpf | Infection, inflammation |
| Eosinophil | ~12-15 μm | Bilobed, requires special stain | Absent | Drug hypersensitivity nephritis |
| Lymphocyte | ~8-10 μm | Small, dark round nucleus | Few | Chronic inflammation, rejection |
| Squamous epithelial | Large (40+ μm) | Flat, abundant cytoplasm, small nucleus | Few | Contamination marker |
| Transitional epithelial | 40-200 μm | Pear-shaped, endo-ecto rim | Few | Sheets = r/o malignancy |
| Renal tubular epithelial | 12-60 μm | Granular cytoplasm, eccentric nucleus | Rare | Tubular injury (ATN) |
Practical Tips
- Examine urine fresh - cells lyse within 2 hours at room temperature
- Refrigerate (2-8°C) to preserve cells if delay is unavoidable
- Acetic acid helps differentiate degenerating neutrophils from tubular cells (enhances nuclear lobulation)
- Phase-contrast microscopy improves detection of hyaline casts and translucent structures
- Pyuria in hypotonic urine - use leukocyte esterase strip to confirm (cells lyse rapidly)
- Distinguishing neutrophils from RTECs in degenerating specimens can be aided by the peroxidase cytochemical reaction (neutrophils are peroxidase-positive)
Source: Henry's Clinical Diagnosis and Management by Laboratory Methods, Chapter 29 - Examination of Urine Sediment