Microscopic Examination of CRYSTALS

Crystals in Sediment

• precipitation of solutes

• are not normally present in freshly voided urine

• can precipitate on storage

• most are not clinically significant

• pH critical to differentiating some important crystals

Acidic Urine Includes…

All clinically significant crystals are found in acid urine

• Include: cystine, tyrosine, leucine & iatrogenic crystals: sulfonamide & ampicillin

• Amorphous Urates

Amorphous Urates

• Non crystalline urate salts of Na, K, Mg, & Ca

• small & yellow-brown granules and can be in acidic or neutral urine

• Will dissolve in alkaline or when heated

  • If add acetic acid, uric acid crystals will precipitate out

Amorphous Urates vs Amorphous Phosphates

Amorphous urates are non-crystalline urate salts, small yellow-brown granules found in acidic or neutral urine, whereas amorphous phosphates are non-crystalline forms of calcium and magnesium phosphates that typically occur in alkaline urine.

Uric Acid Crystals

• Urine pH = 5.0 to 5.5

• Common form = diamond shape but may be cube shaped or cluster in rosettes

• Usually yellow to orange-brown

• Are birefringent under polarizing light

When do Uric Acid Crystals appear?

Can appear normally BUT can see large #s in gout & increased purine metabolism such as cytotoxic drugs

What are the two forms that Oxalate Crystals appear as?

Both colorless

• Dihydrate Form:

  • 2 pyramids / squares w/ intersecting lines

• Monohydrate Form:

  • small ovoid or dumb bell

Calcium oxalate Dihydrate Form

Usually octahedral or look like envelope, less common than monohydrate form although both are seen in kidney stones

Calcium oxalate Monohydrate Form

A birefringent, colorless crystal that varies in size, often seen in neutral or acidic urine. It can appear due to normal dietary intake (e.g., ascorbic acid, tomatoes, spinach) and also indicates ethylene glycol.

Bilirubin Crystals: Abnormal State

• Appear as fine needles, granules, or plates

• urine is acidic

• always yellow-brown

• the bile stains the other components of the sediment

• presence of the crystals indicate high concentrations of bilirubin in the urine

What is the next step when bilirubin crystals are suspected in urine?

Confirm the presence of bilirubin with a strip reaction; positive results indicate a pathological process and abnormal crystals, often associated with liver disease.

Amino Acid Crystals and Pathology

Amino acid crystals are ALL ABNORMAL & seen in overflow aminoaciduria

• can be seen in rare cases of liver disease, more likely to reflect inherited metabolic disorder

• Include: TYROSINE, LEUCINE, AND CYSTINE

Tyrosine Crystals

• fine, delicate needles, colorless or yellow

• frequently in clusters or sheaves [as in stacks of wheat]

• in acidic urine

• less soluble than leucine, so found more often

Leucine Crystals

• Highly refractile yellow to brown spheres in acid urine.

• Have concentric/radial striations on their surface

• Can be mistaken for fat globules [or vice versa]

  • will not stain with fat stains or appear as maltese cross under polarization

Cystine Crystals

• Colorless hexagonal plates

• sides may be uneven

• primarily seen in acidic urine

• Clincally significant, seen in congenital cystinosis or cystinuria

  • Deposit out in tubules as calculi/stone causing damage

Why are Cystine Crystals confused with Uric Acid Crystals? How do we confirm Cystine Crystal presence?

both may present as hexagonal shapes. To confirm cystine crystal presence, perform cyanide-nitroprusside test using SODIUM CYANIDE which will yield a positive result for cystine (purple color)

Cholesterol Crystals

• Clear flat rectangular plates with notched corners

• in acidic urine

• Rarely seen

• Presence indicates both ideal conditions for precipitation & supersaturation

When are Cholesterol Crystals commonly seen?

• Always see with positive protein + fat droplets, fatty casts or oval fat bodies

• Seen in nephrotic syndrome & other renal damage

Ampicillin Crystals

• Appear in acidic urine

• Require large dosage for formation, so rarely seen

Calcium Phosphate Crystals

Colorless, thin, star-shaped prisms with one tapered end; they often appear as irregular granular sheets resembling degenerating squamous epithelial cells.

Sulfonamides Crystals

• Highly refractile & birefringent

• In acidic urine

• Closely resemble ammonium biurate but differentiated on

  • pH & solubility

  • chemical confirmatory test

• Type varies with form of drug prescribed

• rarely seen due to recent solubility of sulfa drugs

Alkaline Urine Crystals

• Amorphous Phosphate

  • precipitate white rather than pink-orange of amorphous urate

  • presence enhanced by refrigeration

• Triple Phosphate

  • most common are 3 & 6 sided ‘coffin lids’, vary in size

Amorphous Phosphate

• alkaline or neutral urine

• microscopically not distinguishable from amorphous urates

  • distinguishable on urine pH & solubility

  • precipitate white rather than pink-orange of amorphous urates

  • are soluble in acid & will not dissolve when heated to 60C

• presence enhanced by refrigeration

Triple Phosphate Crystals

• Colorless & in different forms

  • most common are 3 & 6 sided ‘coffin lids’

  • vary greatly in size

  • may also see a ‘fern leaf’ form, feathery

• See in normal healthy individuals but are often present in formation of calculi

  • are associated with UTI

Ammonium Biurate

• Yellow brown spheres with striations

• Can have irregular spicules ‘thorny apple’

• In alkaline or neutral urine

• Not significant unless seen in fresh urine

• Usually seen in old specimens

• Dissolve in acetic acid or heating to 60C

Calcium Carbonate

• Very small granular crystals

• Can be misidentified as bacteria

• Usually found in pairs ‘dumbbell shape’

Acidic Urine (pH < 7) Crystals

• Amorphous Urates

• Uric Acid

• Calcium Oxalate

• Bilirubin

• Tyrosine

• Leucine

• Cystine

• Cholesterol

• Sulfonamides

• Ampicillin

Alkaline Urine (pH > 7) Crystals

• Amorphous Phosphates

• Triple Phosphate

• Ammonium Biurate Crystals

• Calcium Phosphate Crystals

• Calcium Carbonate Crystals

What crystal can appear in acidic AND neutral pH?

Calcium Oxalate Crystals

Clinical Significance of Crystals

• kidney stone formation: Calcium oxalate, Uric acid, Cystine, Triple phosphate

• metabolic disorders: Cystine, Tyrosine, Leucine

• liver disease: Bilirubin, Tyrosine, Leucine, Cholesterol

• UTI: Triple phosphate

• drug therapies: Sulfonamides, Ampicillin

• benign: Amorphous urates, Amorphous phosphates

Shapes of Crystals

• Envelope-shaped = Calcium oxalate dihydrate

• Needle-shaped = Uric acid, Bilirubin, Tyrosine, Sulfonamides, Ampicillin

• Hexagonal = Cystine

• "Coffin lid" = Triple phosphate

• "Thorny apple" = Ammonium biurate

• Rhombic = Uric acid

• Spherical = Leucine