Histology and Urinalysis Quiz

Urinalysis Benchtop Reference Guide

• This guide provides an illustrated reference for cell morphology in urinalysis
• It covers various components, including urinary cells, casts, and crystals

Urinary Cells

• Erythrocyte:

  • Appearance: Pale, yellow-orange discs; in hypotonic solutions, they appear colorless "ghost" shapes. In hypertonic solutions, they appear crenated (irregular surfaces).
  • Size: 7-8 µm
  • Special Features: Presence of a few RBCs (<3/high-power field) is normal; increased numbers indicate kidney/urinary tract disease or menstrual blood contamination. Must differentiate from oil droplets (highly refractile) and yeast cells (smaller, oval to round, budding).

• Erythrocyte, Dysmorphic:

  • Appearance: Variable; similar to normal erythrocytes, but with irregular cytoplasmic boundaries/blebs (sometime appearing as "Mickey Mouse ears"), altered central pallor (codocytes, stomatocytes, acanthocytes, etc.)
  • Size: 7-8 µm
  • Special Features: Loss of limiting membrane, indicative of glomerular bleeding (like glomerulonephritis)

• Leukocyte (Neutrophil, Eosinophil, Lymphocyte):

  • Appearance: Colorless on unstained slides; neutrophils show cytoplasmic granulation with nuclear segmentation (though degeneration may result in a single nucleus); eosinophils are larger than neutrophils and lymphocytes are smallest; lymphocytes have agranular cytoplasm.
  • Size: -Neutrophil: 12 µm
    • Eosinophil: 10-15 µm
    • Lymphocyte: 7-15 µm
  • Special Features: Less than five neutrophils/high-power field may be normal; increased neutrophils associated with infection; >1% eosinophils associated with interstitial nephritis; rare lymphocytes can increase after renal transplantation.

• Monocyte/Macrophage:

  • Appearance: Variable; ranging from monocyte morphology to activated macrophages, with abundant cytoplasm that may appear frayed or contain vacuoles, granules, or ingested debris; lobulated band-like/bean-shaped nucleus.
  • Size: 14-30 µm (larger than neutrophils)
  • Special Features: Ingested material (lipid, etc.) may be present; often seen in chronic inflammation and radiation therapy.

• Renal Tubular Epithelial (RTE) Cell:

  • Appearance: Polyhedral shape, granular cytoplasm, and often eccentric nucleus; surface may be frayed; microvilli present.
  • Size: 20-35 µm
  • Special Features: Line kidney nephron; their presence indicates renal tubular damage (acute tubular necrosis, viral infection, or renal transplant rejection); differentiate from neutrophils, mononuclear leukocytes, and transitional epithelial cells. Evaluate for viral inclusion bodies. Fat droplets ("oval fat bodies") characteristically show "Maltese cross" on polarization; use Oil Red O or Sudan stain for confirming lipid presence; Prussian blue stain for iron/hemosiderin confirmation.

• Spermatozoa:

  • Appearance: Sperm head smaller and narrower than erythrocyte; a long slender tail, which may detach.
  • Size: 2-6 µm (head); 40-60 µm (tail)
  • Special Features: Found in men with retrograde ejaculation, post-prostatectomy, or samples collected soon after ejaculation.

• Squamous Epithelial Cell:

  • Appearance: Large cell with abundant cytoplasm; small nucleus; well-defined cell membrane often with occasional curled or folded edges; occasionally binucleated; may show cytoplasmic swelling, frayed borders, or 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 indicate contamination.

• Transitional Epithelial Cell (urothelial cell):

  • Appearance: Round to pear shape with central, well-defined, and oval to round nucleus and well-defined cytoplasmic borders; cytoplasmic ratio higher than squamous cells; can occur singly, in pairs, or in clusters; may show cytoplasmic processes ("tadpole cells").
  • Size: Variable (40-200 µm)
  • Special Features: Line renal pelvis, ureters, and bladder (in males, also proximal urethra). Normal constituent of urine; increased numbers associated with infection, renal stones, bladder cancer, and post-catheterization.

Urinary Casts

• Fatty Cast:

  • Appearance: Cylindrical to cigar-shaped, rounded or blunt ends, containing large numbers of spherical, highly refractile fat droplets; may form oval fat bodies.
  • Special Features: Associated with marked proteinuria, acute tubular necrosis or nephrotic syndrome; highly refractile and may show birefringence ("Maltese cross" pattern).

• Cellular Cast (RTE or Neutrophil):

  • Appearance: Contains intact or partially disrupted cells (RTE or neutrophils) in a cylindrical/cigar-shaped matrix.
  • Special Features: Associated with kidney diseases (especially acute tubular necrosis or renal transplant rejection); distinguished from other casts by cellular components.

• Granular Cast:

  • Appearance: Elongated cylinders with smooth margins and evenly dispersed fine to coarse spherical granules.
  • Special Features: Found in normal urine and renal disease, notably stress/strenuous exercise or renal disease; can be confused with hyaline or fatty casts but do not polarize and are refractile.

• Hyaline Cast:

  • Appearance: Colorless, homogeneous, and translucent; cigar-shaped with smooth or finely wrinkled surface, smooth lateral margins, and rounded or tapered ends. Can be coiled or tortuous.
  • Special Features: Common in normal urine and renal diseases and often associated with stress/physiological stress.

• Erythrocyte (Red Blood Cell) Cast:

  • Appearance: Cylindrical to cigar-shaped with rounded ends; uniformly sized red blood cells densely or loosely cover the hyaline or granular matrix. May appear yellow-red. - Special Features: Indicate renal disease such as acute nephritis, glomerular injury, or malignant hypertension.

• Waxy Cast:

  • Appearance: Cylindrical shape, usually broad and stubby; possible serrated, notched, or indented lateral margins; cracked; relatively homogenous, appearing waxy or gel-like.
  • Special Features: Associated with severe or progressive renal disease and acute glomerulonephritis

Urinary Crystals at Acid pH

• Cystine Crystals:

  • Appearance: Clear, colorless, hexagonal form; significant variation in crystal size; weak birefringence when viewed using polarized light.
  • Special Features: Present in large numbers in individuals with cystinosis (congenital, autosomal recessive condition); most common cause of aminoaciduria; diagnosis confirmed via cyanide-nitroprusside test and chromatography/amino acid analysis.

• Sulfonamide Crystals:

  • Appearance: Two types, sulfadiazine (needle-like bundles resembling stacked wheat sheaves, fan shapes, or clumps; have radiating spikes) and sulfamethoxazole (divided or fractured spherical form); dark brown.
  • Special Features: May form renal calculi, particularly in dehydrated individuals but not usually an issue when water-soluble forms are used.

• Uric Acid Crystals:

  • Appearance: Variations in shape (four-sided, wedge, six-sided plates, needles, and stars), usually yellow to brown, strongly birefringent.
  • Special Features: Associated with hyperuricemia, gouty nephropathy, tumor lysis syndrome; differentiates from cystine crystals using birefringence.

• Amorphous Urate Crystals:

  • Appearance: Colorless or red-brown granular aggregates commonly referred to as "brick dust".
  • Special Features: Often found in concentrated urine and correlated with fever or dehydration; differentiated from amorphous phosphates, which occur in alkaline urine.

Urinary Crystals at Neutral or Acid pH

• Bilirubin Crystals:

  • Appearance: Small yellow-brown clusters or clumps resembling spheres with needle-like projections.
  • Special Features: Abnormal in urine and often indicates large amounts of bilirubin and/or bile-stained cells; soluble in various compounds (acetic acid, hydrochloric acid, sodium hydroxide, and acetone).

• Calcium Oxalate Crystals:

  • Appearance: Common dihydrate forms appear as small, colorless octahedrons resembling stars or envelopes (or less common monohydrate forms like dumbbells, ovals, or ellipses). All forms are birefringent.
  • Special Features: Commonly found in diet-rich individuals in oxalic acid (e.g. tomatoes, apples, asparagus).

• Cholesterol Crystals:

  • Appearance: Large, flat, clear, colorless rectangular, or rhomboid plates often with one notched corner; birefringence produces bright hues.
  • Special Features: Rare in fresh urine but can occur with refrigeration; associated with fatty casts, oval fat bodies, and nephrotic syndrome.

• Hippuric Acid Crystals:

  • Appearance: Colorless to pale yellow, frequently appearing as hexagonal prisms, needles or rhombic plates; birefringent.
  • Special Features: Typically found in individuals consuming diets rich in benzoic acid (e.g., vegetables) or associated with acute febrile illness or liver disease.

• Leucine Crystals:

  • Appearance: Highly refractile, brown, spherical crystals with a central nidus and "spoke-like" striations extending to periphery; birefringent but shows a pseudo "Maltese cross" with polarized light.
  • Special Features: Rare, seen in severe liver disease or amino acid metabolism disorders; often appear alongside tyrosine crystals.

• Tyrosine Crystals:

  • Appearance: Silky, fine, colorless to black needles; clumps or sheaves form after refrigeration.
  • Special Features: Rare, associated with leucine crystals in cases of protein metabolism abnormalities like hereditary tyrosinosis or hepatic failure.

Urinary Crystals at Neutral or Alkaline pH

• Ammonium Biurate Crystals:

  • Appearance: Dark yellow or brown spheres with concentric or radial striations, sometimes featuring multiple short to long, irregular projections resembling thorns (commonly referred to as "thorn apples").
  • Special Features: Rare; typically found in alkaline urine that has aged; mimicking crystals; (e.g. sulfamethoxazole, sulfadiazine and leucine).

• Ammonium Magnesium (Triple) Phosphate Crystals:

  • Appearance: Elongated, commonly rectangular, monoclinic prisms with axial symmetry; may assume a fern-like, feathery form as they dissolve; birefringent.
  • Special Features: Commonly associated with bacterial growth.

• Amorphous Phosphate Crystals:

  • Appearance: Fine, colorless or white granules occurring in clumps in alkaline urine.
  • Special Features: Often morphologically identical to amorphous urates; they will not dissolve when heated in a water bath to 60°C.

Organisms

• Bacteria:
  • Appearance: Tiny, colorless, round (cocci) or elongated (bacilli/rods); may occur singly or in chains; clusters
• Yeast/Fungi:
  • Appearance: Oval, colorless, refractile and have single buds; may also exhibit pseudohyphae (branching, non-septated, filamentary structures)
• Miscellaneous/Exogenous
  • Fat Droplet:
    • Appearance: Highly refractile; dark-greenish spherule under low power; clear, globular sphere under high power; show "Maltese cross" when polarized light is used.
  • Fiber (Exogenous)/Fecal Contamination:
    • Appearance: Flat, refractory, colorless; often contain pits, fissures, or cross-striations; can vary greatly in size.
    • Special Feature: Usually originated from clothing, cotton balls, applicator sticks, dressings and disposable diapers.
  • Mucus:
    • Appearance: Translucent; delicate; wavy; intertwined aggregate strands; typically have tapered ends.
    • Special Feature: Mostly found in urinary/vaginal infections.
  • Pollen Grains:
    • Appearance: Large, rounded, or oval with a well-defined, thick cell wall and/or regular/short projections.
    • Special Feature: Contamination from the urine or containers
  • Starch Granules:
    • Appearance: Colorless, birefringent, irregularly rounded; sometimes display a central slit/indentation; "Maltese crosses" with polarized light.
    • Special Feature: Exogenous contaminant often associated with baby powder.