Urinalysis Benchtop Reference Guide PDF

# Urinalysis Benchtop Reference Guide: An Illustrated Guide for Cell Morphology ## Table of Contents ### Urinary Cells 1. Erythrocyte 2. Erythrocyte, Dysmorphic 3. Leukocyte (Neutrophil, Eosinophil, Lymphocyte) 4. Monocyte/Macrophage 5. Renal Tubular Epithelial (RTE) Cell 6. Spermatozoa 7. Squa...

# Urinalysis Benchtop Reference Guide: An Illustrated Guide for Cell Morphology ## Table of Contents ### Urinary Cells 1. Erythrocyte 2. Erythrocyte, Dysmorphic 3. Leukocyte (Neutrophil, Eosinophil, Lymphocyte) 4. Monocyte/Macrophage 5. Renal Tubular Epithelial (RTE) Cell 6. Spermatozoa 7. Squamous Epithelial Cell 8. Transitional Epithelial Cell (Urothelial Cell) ### Urinary Casts 9. Fatty Cast 10. Cellular Cast (RTE or Neutrophil) 12. Granular Cast 13. Hyaline Cast 14. Erythrocyte (Red Blood Cell) Cast 15. Waxy Cast ### Urinary Crystals at Acid pH 17. Cystine Crystals 18. Sulfonamide Crystals 19. Uric Acid Crystals 20. Amorphous Urate Crystals ### Urinary Crystals at Neutral or Acid pH 21. Bilirubin crystals 22. Calcium Oxalate Crystals 23. Cholesterol Crystals 24. Hippuric Acid Crystals 25. Leucine Crystals 26. Tyrosine Crystals ### Urinary Crystals at Neutral or Alkaline pH 27. Ammonium Biurate Crystals 28. Ammonium Magnesium (Triple) Phosphate Crystals 29. Amorphous Phosphate Crystals ### Organisms 31. Bacteria 32. Yeast/Fungi ### Miscellaneous/Exogenous 33. Fat Droplet 34. Fiber (Exogenous)/Fecal Contamination 35. Mucus 36. Pollen Grains 37. Starch Granules 38. Index ## Erythrocyte **Appearance:** Pale, yellow-orange discs in unstained preparations. In hypotonic solutions they can appear as colorless circles or "ghosts" with defined membranes by phase contrast microscopy. In hypertonic solutions they can appear crenated (irregular surfaces). **Size:** 7-8 µm. **Special Features:** The presence of a few erythrocytes, or red blood cells (RBCs), in urine (<3/high-power field) is normal. Increased numbers of RBCs may be seen with kidney/urinary tract disease or menstrual blood contamination. Must differentiate from oil droplets (greater variation in size, highly refractile) and yeast cells (smaller, oval to round, budding). ## Erythrocyte, Dysmorphic **Appearance:** Variable. Similar to normal erythrocytes but with irregular cytoplasmic boundaries/blebs (A, B; two symmetrical blebs are referred to as "Mickey Mouse ears") or altered central pallor, including codocytes (target cells), stomatocytes (elongated central pallor), acanthocytes (spur cells or blunt tipped cytoplasmic projections), etc. **Size:** 7-8 µm. **Special Features:** Loss of the limiting membrane results in an altered erythrocyte appearance. Historically associated with glomerular bleeding, such as glomerulonephritis. ## Leukocyte (Neutrophil, Eosinophil, Lymphocyte) **Appearance:** Colorless on unstained slides. Neutrophils show cytoplasmic granulation (see image) with nuclear segmentation, although degeneration can lead to nuclear fusion and a single nucleus. Eosinophils appear similar to neutrophils but are slightly larger. Lymphocytes are the smallest and have agranular cytoplasm. **Size:** 12 µm = Neutrophil; 10-15 µm = Eosinophil; 7-15 µm = Lymphocyte. **Special Features:** Less than five neutrophils/high-power field may be normal. Increased neutrophils are associated with acute infection. Presence of more than 1% eosinophils is associated with interstitial nephritis. Rare lymphocytes are normally present and transiently can be increased after renal transplantation. ## Monocyte/Macrophage **Appearance:** Variable, ranging from monocyte morphology (as seen in the blood) to activated macrophages. They have abundant cytoplasm that sometimes appears frayed, with cytoplasmic vacuoles, granules, or ingested debris (depicted in image). Stained smears highlight blue-gray cytoplasm with lobulated/band-like/bean-shaped nucleus. **Size:** 14-30 µm. Larger than neutrophils. **Special Features:** Ingested material (digested material, lipid, etc) may be present in the cytoplasm. Monocytes/macrophages are seen with chronic inflammation and radiation therapy. ## Renal Tubular Epithelial (RTE) Cell **Appearance:** Polyhedral shape, with granular cytoplasm and single round nucleus that is sometimes eccentric. Disintegrated cells often have frayed cytoplasm and indistinct cytoplasmic boundaries. Microvilli (depicted in image) can be seen. **Size:** 20-35 µm. **Special Features:** RTEs line the kidney nephron. Their presence in urine is indicative of renal tubular damage (acute tubular necrosis, viral infection, or renal transplant rejection). Difficult to distinguish from degenerated neutrophils, mononuclear leukocytes, and transitional epithelial cells. Evaluate for viral inclusions. Lipid-laden renal tubular cells ("oval fat bodies") show characteristic "Maltese cross" on polarization; confirm lipid with Oil Red O or Sudan stain. Prussian blue stain to confirm iron/hemosiderin. ## Spermatozoa **Appearance:** Sperm head is smaller and more narrow in comparison to an erythrocyte. Sperm have a long slender tail that can become detached. **Size:** 2-6 µm head; 40-60 µm tail **Special Features:** Found in men with retrograde ejaculation, post prostatectomy, or in samples collected soon after ejaculation. ## Squamous Epithelial Cell **Appearance:** Large cell with abundant cytoplasm, small nucleus, and well-defined cell membrane with occasional curled or folded edges. May be binucleated. Degeneration can lead to cytoplasmic swelling, frayed borders, and pyknotic nuclei. **Size:** 30-50 µm, cell size; 10-12 µm, nucleus size. **Special Features:** Derived from female urethra, distal male urethra, skin, or vaginal mucosa. High numbers in urine typically indicate contamination. ## Transitional Epithelial Cell (Urothelial Cell) **Appearance:** Round to pear shape, with central, well-defined, oval to round nucleus and well-defined cytoplasmic borders. Higher nuclear-to-cytoplasmic ratio than squamous cells. Occur singly, in pairs, or in clusters. Occasional cytoplasmic processes ("tadpole cells") indicate prior attachment to basement membrane. **Size:** Variable, 40-200 µm. **Special Features:** Line the renal pelvis, ureters, and bladder. In males, also line the proximal urethra. Normal constituent in urine. Increased numbers are associated with infection, renal stones, bladder cancer, and post catheterization. ## Fatty Cast **Appearance:** Cylindrical to cigar-shaped with rounded or blunt ends containing large numbers of spherical, highly refractile fat droplets of varying size in matrix or forming oval fat bodies (lipid droplets) in the cast (A). **Size:** Variable length and width. **Special Features:** Associated with marked proteinuria, acute tubular necrosis, or nephrotic syndrome. Highly refractile and has unique birefringence. Should be distinguished from cellular and granular casts. Fat may be stained with Sudan stain or examined with polarized light for birefringent "Maltese cross" pattern (B). ## Cellular Cast (RTE or Neutrophil) **Appearance:** Cylindrical/cigar-shaped cast with rounded ends containing intact or partially disrupted cells. If there is a mixture of cells or if morphology is obscured, the term cellular cast may be used. **Cellular Cast, RTE:** Contains intact RTE cells in matrix and on surface. RTE cells have a large, single, central nucleus and relatively sparse, agranular cytoplasm, or they may be pyknotic with granules from degenerated RTE cells. Cast matrix must be present. **Cellular Cast, Neutrophil:** May be crowded with neutrophils or have a few intact cells, often at one end. Nuclei may be degenerated. Prominent granules in cells and matrix are often seen. **Size:** Variable length and width. **Special Features:** Refractile but not birefringent. Identification of cellular nuclei on the surface helps identify cellular components. Distinguish from fatty or coarse granular casts. **Cellular Cast, RTE:** Found in a wide variety of kidney diseases, especially in tubular damage (acute tubular necrosis or renal transplant rejection). **Cellular Cast, Neutrophil:** Most prevalent in pyelonephritis or other inflammatory processes (lupus or allergic nephritis). ## Granular Cast **Appearance:** Elongated cylinders with rounded ends and smooth margins containing many evenly dispersed, fine to coarse spherical granules. Granules may be confined to one area and may vary in size. Casts may appear folded, bent, or twisted. **Size:** Variable length; diameter 25-50 µm. **Special Features:** Found in normal urine as well as renal disease. Less frequent than hyaline casts. Numbers may increase with stress, strenuous exercise, or renal disease. Do not polarize but are refractile. Should be distinguished from hyaline casts and degenerating cellular and fatty casts. ## Hyaline Cast **Appearance:** Colorless, homogeneous, and translucent or nearly transparent, with a low refractive index. Cigar-shaped with a smooth or finely wrinkled surface, smooth lateral margins, and rounded or tapered ends. May also appear tortuous, coiled, or have a long tapered end. Small inclusion granules may be seen in the cast matrix. **Size:** Variable length; diameter 25-50 µm. **Special Features:** Present in small numbers in normal urine, but more prevalent after strenuous physical exercise, physiological stress, and nearly all renal diseases. May be difficult to see without phase microscopy and do not polarize. Distinguish from mucus strands and granular casts. ## Erythrocyte (Red Blood Cell) Cast **Appearance:** Cylindrical to cigar-shaped with rounded ends containing intact, uniformly sized red blood cells (RBCs) that densely or loosely cover the hyaline or granular matrix and the cast surface. RBCs may be shrunken or crenated. A yellow or red-brown color is seen when many RBCs fill the cast. **Size:** Variable length and width. **Special Features:** Infrequently found. Indicate serious renal disease, including acute nephritis, glomerular injury or glomerulonephritis, and malignant hypertension. They are refractile but not birefringent. The reddish color is a useful distinguishing feature. ## Waxy Cast **Appearance:** Cylindrical in shape but usually broad and stubby with blunt ends that may appear broken off or squared. Well-defined parallel margins may be serrated, notched, or indented. Lateral margins often appear cracked. Granules are inconspicuous or absent. Colorless or yellow homogeneous matrix appears waxy or gel like. **Size:** Variable length; broad (>40 µm) diameter. **Special Features:** Associated with severe or progressive renal disease or acute glomerulonephritis. Not found in well individuals. Refractile but nonpolarizing. Must be distinguished from fibers, hyaline casts, and pigmented (bilirubin) casts. ## Cystine Crystals **Appearance:** Clear, colorless, and hexagonal. There may be a wide variation in crystal size. They demonstrate weak birefringence when viewed with polarized light. **Size:** Variable. **Special Features:** These crystals are present in large numbers in patients with cystinosis, a congenital autosomal recessive condition that has a homozygous incidence of about 1:10,000 to 1:13,000. It is the most common cause of aminoaciduria. **Confirmatory test:** Positive cyanide-nitroprusside test. Definitive diagnosis is dependent upon chromatography and quantitative amino acid analysis. ## Sulfonamide Crystals **Appearance:** There are two types of sulfonamide crystals: sulfadiazine and sulfamethoxazole. Sulfadiazine crystals (shown above) appear as bundles of long needles with eccentric binding that resemble stacked wheat sheaves, fan shapes, or spherical clumps with radiating spikes. Sulfamethoxazole crystals are dark brown, divided or fractured spheres. **Size:** Two to three times the size of red blood cells. **Special Features:** May form renal calculi, especially in a dehydrated patient; but with the use of water-soluble sulfonamides, this is infrequently seen today.. ## Uric Acid Crystals **Appearance:** Usually yellow to brown in color and birefringent. Common forms are four-sided, flat, and whetstone. They vary in size and shape, including six-sided plates, needles, lemon-shaped forms, spears (clubs), wedge shapes, and stars. **Size:** Variable. **Special Features:** When hexagonal, use birefringence to distinguish from cystine (uric acid is highly birefringent). Can be associated with hyperuricemia, uric acid stones, tumor lysis syndrome, or gouty nephropathy. ## Amorphous Urate Crystals **Appearance:** These colorless or red-brown aggregates of granular material occur in cooled standing urine. Often referred to as "brick dust." Amorphous urates are morphologically identical to amorphous phosphates occurring in alkaline urine. **Size:** Fine granules. **Special Features:** Found in concentrated urine associated with fever and dehydration. Amorphous urates should be carefully examined for hidden bacteria, casts, or other crystals. ## Bilirubin Crystals **Appearance:** Small, yellow-brown clusters in clumps or spheres with needle-like projections. Bilirubin crystals may precipitate on other formed elements in the urine, such as cells or hyaline casts. **Size:** Variable. **Special Features:** Bilirubin crystals are abnormal in urine. They occasionally are seen in urine containing large amounts of bilirubin, and they usually accompany bile-stained cells. The presence of these crystals should be accompanied by a positive biochemical test for bilirubin. They are soluble in acetic and hydrochloric acids, sodium hydroxide, and acetone. ## Calcium Oxalate Crystals **Appearance:** There are two forms of calcium oxalate crystals. The more common dihydrate forms (shown above) are small, colorless octahedrons resembling stars or envelopes. They appear as two pyramids joined at the base. Monohydrate forms are less often seen. They are dumbbell shaped, elliptical, or oval. All calcium oxalate crystals are birefringent. **Size:** Variable. **Special Features:** Patients who consume foods rich in oxalic acid, such as tomatoes, apples, asparagus, oranges, or carbonated beverages, may have these crystals in their urine. Although usually not abnormal, they may suggest the etiology of renal calculi. These crystals are soluble in 90% ethyl alcohol and in dilute hydrochloric acid. ## Cholesterol Crystals **Appearance:** Large, flat, clear, colorless, and rectangular plates or rhomboids that often have one notched corner (A). Cholesterol crystals polarize brightly (B), producing a mixture of many brilliant hues within each crystal. **Size:** Variable. **Special Features:** Cholesterol crystals are extremely rare in fresh voided urine, but they can be seen upon refrigeration. When present, they are frequently accompanied by fatty casts and oval fat bodies. Cholesterol crystals are considered pathologic. Their presence is associated with nephrotic syndrome. Radiographic contrast media has a similar appearance to these crystals; however, the urine specific gravity is high after administration of contrast media. ## Hippuric Acid Crystals **Appearance:** Colorless to pale yellow and may occur as hexagonal prisms, needles, or rhombic plates. They are birefringent when examined with polarized light. **Size:** Variable. **Special Features:** These crystals are a rare component of acid urine. They are typically found in persons who eat a diet rich in benzoic acid, such as one rich in vegetables, but they may also be seen in patients with acute febrile illnesses or liver disease. Hippuric acid crystals are soluble in sodium hydroxide and alcohol.. ## Leucine Crystals **Appearance:** These highly refractile, brown, spherical crystals have a central nidus and "spoke-like" striations extending to the periphery (A). Leucine spherules are birefringent, demonstrating a pseudo "Maltese cross" appearance with polarized light (B). **Size:** Variable. **Special Features:** Leucine crystals are extremely rare. They can be seen in severe liver disease and certain disorders of amino acid metabolism. They often appear in association with tyrosine crystals. Leucine crystals are soluble in sodium hydroxide and hot acetic acid. ## Tyrosine Crystals **Appearance:** Silky and fine, colorless to black needles, depending on microscopic focusing. Clumps or sheaves form after refrigeration. **Size:** Variable. **Special Features:** Tyrosine crystals are rare, and they usually appear in the urine sediment with leucine crystals. Both are products of protein metabolism. Tyrosine crystals may be seen in hereditary tyrosinosis or with hepatic failure. They are soluble in hydrochloric acid, sodium hydroxide, and boiling water. ## Ammonium Biurate Crystals **Appearance:** Dark yellow or brown spheres with concentric or radial striations and multiple short to long, irregular projections resembling thorns. Sometimes referred to as "thorn apples." Strongly positive birefringence. **Size:** Variable. **Special Features:** These crystals are rare in fresh urine. They may be seen in alkaline urine that has aged for days, weeks, or months (eg, in teaching specimens). Mimics, such as sulfamethoxazole, sulfadiazine, and leucine, occur in acid urine. Ammonium biurate crystals are of no clinical significance. ## Ammonium Magnesium (Triple) Phosphate Crystals **Appearance:** Referred to as "coffin lids" (B), these appear as elongated, usually rectangular, monoclinic prisms (A) with axial symmetry. Rarely, they assume a fern-like feathery form as they dissolve. Positive birefringence. **Size:** Variable. **Special Features:** These are considered a normal component of urine, but they may be associated with bacterial growth. Struvite calculi seen in some patients with chronic urinary tract infection are composed of triple phosphate crystals. ## Amorphous Phosphate Crystals **Appearance:** Fine, colorless, or white granules occurring in clusters/clumps in alkaline urine. Amorphous phosphates are morphologically identical to amorphous urates occurring in acid urine. **Size:** Fine granules. **Special Features:** Unlike amorphous urates, phosphates will not dissolve when heated in a water bath to 60°C. These crystals are of no clinical significance. Amorphous phosphates should be carefully examined for hidden bacteria, casts, or other crystals. ## Bacteria **Appearance:** Usually seen as tiny, colorless, round (cocci), or elongated (bacilli, rods) shapes. May be single but often occur in clusters or chains. **Size:** Individual bacteria are about 1 µm. **Special Features:** May be confused with calcium carbonate or amorphous urate/phosphate crystals. Bacteria are more round and regular in size and shape than these crystals. Bacteria may represent a urinary tract infection, particularly if neutrophils are numerous, or they may be a vaginal or fecal contaminant. ## Yeast/Fungi **Appearance:** Candida albicans can appear as budding yeast or pseudohyphae. Yeast are ovoid, colorless, refractile, and slightly smaller than red blood cells, and they often have a single smaller bud. Pseudohyphae are branching, nonseptate, and filamentous structures with nonparallel sides; they often have terminal budding. **Size:** Yeast are 5-7 µm; Pseudohyphae may be up to 50 µm long. **Special Features:** Budding yeast and pseudohyphae may be vaginal contaminants. However, pseudohyphae can represent a serious bladder or kidney infection. ## Fat Droplet **Appearance:** Highly refractile, dark-greenish spherule under low-power magnification; clear, globular sphere of varying size under high power (A). Fat droplets show a "Maltese cross" appearance when polarized (B). **Size:** Variable; occasionally assume large, amorphous, irregular shapes. **Special Features:** A wide variety of exogenous and endogenous materials can result in fat droplets being found in the urinary sediment. Exogenous sources include mineral oil, catheter lubricants, or vaginal creams. Endogenous sources include fat-laden cells or casts, and they are usually found in patients with nephrotic syndrome. ## Fiber (Exogenous)/Fecal Contamination **Appearance:** Exogenous fibers are usually well-defined, flat, refractile, and colorless and often contain fissures, pits, or cross-striations. These may be small, single plant cells, vegetable hairs, or a variety of exogenous fibers. **Size:** Usually large; varies considerably depending on the type of fiber. Vegetable hairs may be 30 µm or longer. Skeletal muscle fibers may be three to four times the size of broad waxy casts. **Special Features:** Fibers include hair and synthetic and natural fibers from clothing, cotton balls, applicator sticks, dressings, and disposable diapers. ## Mucus **Appearance:** Translucent, delicate strands that may form long, wavy, and intertwined aggregates. Although they may resemble hyaline casts, strands of mucus are more irregular in shape than casts and typically have tapered ends. **Size:** Varies considerably. **Special Features:** The presence of mucus in the urine is most commonly associated with infections involving the lower urinary and vaginal tracts. They constitute the background material in the field, and they are more obvious with phase microscopy. ## Pollen Grains **Appearance:** Pollen grains are large, rounded, or oval and have a well-defined, thick cell wall. They may have short, regular, and thorny projections. Some are yellowish-tan. They may resemble parasite ova. **Size:** 20 µm or greater in diameter. **Special Features:** Pollen grains contaminate urine and urine containers, often on a seasonal basis. ## Starch Granules **Appearance:** Starch granules are colorless, birefringent, and irregularly rounded with a central slit or indentation (A). They have been described as looking like a beach ball. With crossed polarizing filters, the granules form white "Maltese crosses" against a black background (B). **Size:** Vary in size from that of a red cell (7-8 µm) to as much as six times larger. **Special Features:** Because starch is present in baby powder and may be used to powder surgical gloves or other common materials, these granules are the most common exogenous finding in urine sediment.