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Urine Crystals (Crystalluria)

April 17, 2022Lab TestsUrine Analysis

Urine Crystals (Crystalluria)

Sample for urine crystals

  1. Freshly voided urine is the best sample.
  2. Refrigerate or if you keep it at room temperature that will increase the formation of the crystals.

Precautions for urine crystals (Crystluria)

  1. pH is very important to note.
  2. Taking the history of the medications will save time and energy.
  3. Refrigeration will precipitate out many crystals, because of the change in the solubility of various crystals.
  4. Urine kept at room temperature leads to precipitation or dissolves the crystals.
  5. The radiographic dye can make crystals in dehydrated patients.
  6. Ampicillin and sulfonamides also give rise to crystal formation, this happens in dehydrated patients.

Definition of urine crystals (Crystlluria)

  1. There may be well-defined crystals or amorphous material in the urine sediment.
  2. These appear as geometrical formed structures or amorphous materials.
  3. The presence of crystals in the urine is called Crystalluria.
  4. When urine is left at room temperature or refrigerated then urine becomes cloudy because of the precipitation of crystals or amorphous material.

Importance of the urine crystals (crystalluria):

  1. These crystals are important in the case of kidney stones.
  2. Renal damage was caused by the crystals.
  3. In liver diseases.
  4. Inborn error of metabolism.
  5. Some of the crystals indicate some metabolic disorders like cystinuria or a sulfa drug.
  6. The stone formation may be without crystals in the urine or crystalluria may be without stone formation.
  7. Crystals are seen mostly in concentrated urine.
  8. Crystals are divided into :
    1. Normal  or abnormal
    2. In alkaline or acidic urine.
    3. Crystals were found due to medication.
  9. Crystals found in acidic urine have a pH of <6.5 and in alkaline urine pH is >7.0.

Reporting of the crystalluria:

  1. Rare/HPF.
  2. FeW/HPF.
  3. Moderate/HPF.
  4. Many/HPF.

Mechanism of the formation of urine crystals:

  1. Kidneys are the main site for the excretion of the waste product of metabolism which is needed by the body.
    1. Urea is from the metabolism of the amino acid.
    2. Creatinine from the muscles.
    3. Uric acid from the nucleic acid.
    4. The hemoglobin end product is bilirubin.
    5. Hormones are excreted as hormone metabolites.
    6. kidneys also excrete the toxins, and other foreign substances produced by the body or ingested, such as pesticides, drugs, and food additives.
  2. Crystals are formed by the crystalization of urine solutes.
  3. The solutes are:
    1. Inorganic salts.
    2. Organic compounds.
    3. Medications by drug use.
  4. Precipitation is dependent upon:
    1. Temperature.
    2. pH.
    3. Solute concentration.
      1. As the concentration of solutes increases, their ability to remain in solution decreases and result in crystal formation.
      2. Solute precipitate more readily at low temperatures.
    4. So if you keep the urine at room temperature or refrigerate it, then crystals are abundant.
  5. Organic and iatrogenic compounds crystalize more easily in the acid urine.
  6. Inorganic salts are less soluble in neutral or alkaline pH.
    1. The exception is calcium oxalate which precipitates in both acidic and alkaline mediums.
  7. The Slower crystalization leads to larger crystal formation but the basic structure remains the same.
  8. Reversal of the pH will dissolve the crystals.
  9. Amorphous urates crystals formed in the refrigerated sample, if you warm the urine these will disappear.
  10. Amorphous phosphate crystals need acetic acid to dissolve. But practically this is not done because the acetic acid will distort the RBCs.

Helping point in Reporting the crystals:

  1. Always note the pH of the urine which will help to identify the crystals.
  2. All abnormal crystals are found in acidic urine.
  3. Polarized microscopy also helps to identify the crystals.

Characteristics of crystals:

  1. Most of the urate crystals are yellow to reddish-brown.
  2. Amorphous urates appear in yellow-brown granules. these are in clumps and look like the granular cast.
  3. If urine is refrigerated then the amorphous urates crystals precipitate and give pink sediment.
  4. Amorphous urates crystals appear in the urine with low pH >5.5 and uric acid crystals appear when pH is lower.

Various types of crystals in acid urine:

Acidic- urine crystals are:

  1. Uric acid.
  2. Amorphous urates.
  3. Sodium urates.
  4. Cystine (these are rarely found).
  5. Cholesterol crystals (these are rarely found).
  6. Tyrosine (these are rarely found).
  7. Leucine (these are rarely found).
  8. Bilirubin.

Uric acid:

  1. Serum uric acid is raised in 40 to 50% of the patients.
  2. These are seen in a variety of shapes like four-sided flat plates, wedge-shaped, and rosettes.
  3. These are usually yellow-brown in color.
  4. But maybe colorless and six-sided shapes like cystine crystals.
  5. these are birefringent in polarized light.
  6. These are common in patients with leukemia getting chemotherapy.
  7. Sometimes these are seen in gout.
Urine uric acid crystals

Urine uric acid crystals

Acid urates and sodium urates:

  1. These are like amorphous urates and are seen in less acidic urine.
  2. These are seen along with amorphous urates and have little clinical significance.
  3. Sodium urates crystals are needle-shaped and are seen in the synovial fluid during the attack of gout and also appear in the urine.

Amorphous urates:

  1. These are yellow-brown granules.
  2. These may appear in clumps resembling granular cast.
  3. These are brick dust or yellow-brown.
  4. These crystals are found in acidic urine with a pH>5.5 (acidic urine).
  5. These are soluble in an alkaline medium.
Urine amorphous urates

Urine amorphous urates

Calcium oxalate:

  1. More common in acid urine, but may be seen in neutral or even in alkaline urine.
  2. The most common is dihydrate, which is a colorless, octahedral envelope shape or two pyramids joined together at their bases.
  3. Monohydrate crystals are oval or dumble-shaped.
  4. In polarized light both are birefringent.
  5. The finding of clumps of calcium oxalate crystals indicates renal stone formation.
  6. These are commonly seen when taking foods like tomato, asparagus, and ascorbic acid.
  7. Monohydrate crystals are seen in ethylene glycol  (antifreeze) poisoning.
  8. These are soluble in dilute hydrochloric acid.
Urine calcium oxalate crystals

Urine calcium oxalate crystals

Crystals in the acidic urine :

Name of crystals   pH Effect of heating  (solubility) Shape  Color 
Sodium urate acidic (<acidic) soluble at 60 C amorphous Colorless to yellow, Amorphous, or large granules
Uric acid acidic <5.5 alkali-soluble rhombic, four-sided flat plates yellow-brown
Amorphous urates acidic >5.5  alkali and heat amorphous or sand-like Microscopically  yellow-brown and occurs in clumps
Sodium urates Acidic
Calcium oxalate acidic or alkaline  dilute HCL enveloped shaped, dumbbell-shaped The colorless octahedral envelope or two pyramids joined at the base.
Cystine acidic  Dilute  HCl acid hexagonal Colorless
Cholesterol acidic Chloroform rectangular, notched plates Colorless
Tyrosine acid/neutral Alkali or heat needles shape form clumps or rosettes Colorless to yellow, needles
Leucine acidic /neutral Hot alkali or alcohol spheres with a concentric circle or  radial striations yellow-brown
Bilirubin acid

Acetic acid, HCL,

ether or chloroform

clumped  needles or granular yellow color
Sulphonamide acid/neutral Acetone Rosette form, needle, colorless to yellow-brown
Ampicillin acid/neutral in needles form colorless
Radiographic dye acid 10% NaOH like cholesterol colorless
Calcium oxalate and uric acid crystals

Calcium oxalate and uric acid crystals

Various types of crystals in alkaline urine:

Alkaline urine crystals are:

  1. Calcium phosphate.
  2. Amorphous phosphates.
  3. Calcium carbonate.
  4. Ammonium biurate.
  5. Tripple phosphate.

Amorphous phosphate:

  1. These are granular in shape like amorphous urates.
  2. If refrigerated then these produce white precipitate which does not dissolve on warming.
  3. These are differentiated from the urates by color and the pH of the urine.
  4. These are soluble in an alkaline or neutral medium.
  5. These are soluble in dilute acetic acid.
Urine Amorphous phosphates crystals

Urine Amorphous phosphates crystals

Triple phosphate (Ammonium magnesium phosphate):

  1. These are seen in alkaline urine.
  2. These are colorless, prism-shaped, resembling the coffin lid.
  3. Under polarized lights are birefringent.
  4. These have no clinical significance.
  5. These are seen in an alkaline medium.
  6. These are soluble in dilute acetic acid.
Urine triple phosphate

Urine triple phosphate

Calcium phosphate:

  1. These are colorless, flat rectangular plates.
  2. Or thin prism and often in rosette forms.
  3. Rosette forms need to be differentiated from the sulphonamides crystals.
  4. These crystals dissolve in dilute acetic acid while sulphonamides crystals will not.
  5. These have no clinical significance.
  6. These are seen inpH of alkaline or neutral.
  7. These are soluble in dilute acetic acid.
Urine calcium phosphate crystals

Urine calcium phosphate crystals

Calcium carbonate:

  1. These are small. colorless, with a dumbbell or spherical shapes.
  2. These may occur in clumps and resemble amorphous material.
  3. If you add acetic acid, then there is gas formation.
  4. In polarized light are birefringent and this differentiates from the bacteria.
  5. Thes crystal has no clinical significance.
  6. These crystals are seen in an alkaline medium.
  7. These are soluble in acetic acid with gas formation.
Urine calcium carbonate crystals

Urine calcium carbonate crystals

Ammonium biurates:

  1. These have characteristic yellow-brown colors.
  2. These are usually described as thorny apples, because of the spicule-covered spheres.
  3. These dissolve at 60 °C.
  4. If you add glacial acetic acid, then these will change into uric acid.
Urine ammonium biurates crystals

Urine ammonium biurates crystals

Crystals in alkaline urine :

Name of crystals pH Effect of heat Color and shape 
Amorphous phosphates Alkaline Remain insoluble Granular
Triple phosphates Alkaline Colorless and prism-shaped like a coffin lid
Calcium phosphate Alkaline Remain insoluble Colorless, flat rectangular plates or thin prisms often in rosettes
Calcium Carbonate Alkaline Small, colorless with a dumbbell  or spherical shape, may occur in clumps and resemble amorphous material
Ammonium biurate Alkaline Dissolve at 60 °C Yellow-brown color, thorny apples
Amorphous urates and triple phosphate

Amorphous urates and triple phosphate

The solubility of crystals:

Crystals  Color pH Soluble in
Calcium oxalate Colorless Acid/neutral Dilute  HCl acid
Uric acid Yellow-brown Acid Alkali
Amorphous urates Brick dust or yellow-brown Acid Alkali and when heated
Tripple phosphate Colorless Alkaline Dilute acidic acid
Amorphous phosphate White-colorless Alkaline/neutral Dilute acid acid
Calcium phosphate Colorless Alkaline/neutral Dilute acidic acid
Calcium carbonate Colorless Alkaline Acetic acid
Ammonium biurate Yellow-brown Alkaline Acetic acid with heat

Abnormal crystals:

  1. Metabolic origin:
    1. Tyrosine.
    2. Cystine.
    3. Cholesterol.
    4. Leucine.
    5. Bilirubin.
    6. Hemosiderin.
  2. Drugs origin:
    1. Sulfonamides.
    2. Radiographic contrast media.
    3. Ampicillin.

Cystine crystals:

  1. These are seen in the inborn error metabolic disorder when the cystine is not absorbed by the renal tubules (cystinuria).
  2. There is a tendency to form renal calculi.
  3. These are colorless, hexagonal plates and may be thick or thin.
  4. In the presence of ammonia, there is the disintegration of these crystals.
  5. Cysteine stones are seen in 1 to 2% of the cases.
  6. The cyanide-nitroprusside test is needed to confirm the cystine crystals.
  7. These crystals appear in an acidic medium.
  8. It is soluble in ammonia and dilute HCL.
Urine Cystine crystals

Urine Cystine crystals

Cholesterol crystals:

  1. These are not seen unless the urine is refrigerated.
  2. These have a characteristic appearance resembling the rectangular plates with a notch in one or more corners.
  3. These are seen as disorders producing lipiduria in nephrotic syndrome, along with fatty acids and oval fat bodies.
  4. In polarized light, these are birefringent.
  5. This crystal appears in an acidic medium.
  6. These are soluble in chloroform medium.
Urine Cholesterol crystals

Urine Cholesterol crystals

Sulfonamide crystals:

  1. There are a variety of crystal shapes and colors.
  2. Shapes variable like needles, whetstone, rhombic, wheat, and rosette with color ranging colorless to yellow-brown,
  3. The history of the patient will help you to diagnose these crystals.
  4. Diazo reaction can confirm these crystals.
  5. These crystals are seen in an acid/neutral medium.
  6. These crystals are soluble in acetone.
Urine sulfa drug crystals

Urine sulfa drug crystals

Tyrosine crystal:

  1. These are fine colorless to the yellow needle-like structures which form clumps or rosettes.
  2. These may be seen in inherited disorders of amino acid metabolism.
  3. These crystals are formed in an acid/neutral medium.
  4. These crystals are soluble in alkali or by heat.
Urine Tyrosine crystals

Urine Tyrosine crystals

Leucine crystals:

  1. These are seen because of the defect in the amino acid, leucine.
  2. These are yellow-brown spheres that will show concentric circles and radial striations.
  3. These are also called wagon wheels.
  4. These crystals form in an acid/neutral medium.
  5. These are soluble in hot alcohol and alkali.
  6. These are less frequent than the tyrosine crystals.
  7. These are accompanied by tyrosine crystals.
Urine Leucine crystals

Urine Leucine crystals

Bilirubin Crystals:

  1. Bilirubin crystals are present in liver diseases where there is an increased amount of bilirubin excreted in the urine.
  2. These crystals are clumped needles or granules with the characteristic color of the bilirubin as yellow.
  3. The chemical reaction for the bilirubin is positive.
Urine Bilirubin crystals

Urine Bilirubin crystals

Radiographic material crystals:

  1. These crystals are colorless.
  2. These crystals appear in an acid medium.
  3. These crystals are soluble in 10% NaOH.
Urine radiographic dye crystals

Urine radiographic dye crystals

Significance of crystals:

  1. Calcium oxalate crystals in clumps indicate renal stone formation.
  2. Calcium oxalate crystals are abundant in food with high oxalic acid like tomatoes, asparagus, and ascorbic acid.
  3. Monohydrate oxalate crystals are seen in ethylene glycol poisoning (antifreeze material).
Urine analysis summary

Urine analysis summary

Normal urine picture:

Physical features Chemical features Microscopic findings
  1. Color = Pale yellow or amber
  2. Appearance = Clear to slightly hazy
  3. pH = 4.5 to 8.0
  4. Specific gravity = 1.015 to 1.025
  1. Blood = Negative
  2. Glucose = Negative
  3. Ketones= Negative
  4. Protein = Negative
  5. Bilirubin = Negative
  6. Urobilinogen = Negative (±)
  7. Leucocyte esterase = Negative
  8. Nitrite for bacteria = Negative
  1. RBCs = Rare or Negative
  2. WBC = Rare or Negative
  3. Epithelial cells = Few
  4. Cast = Negative (Occasional hyaline)
  5. Crystal = Negative (Depends upon the pH of the urine)
  6. Bacteria = Negative

Contamination and artifacts:

There are a few contaminants that interfere with the microscopy of the sediments:

  1. Starch.
  2. Fibers including diaper fibers.
  3. Oil droplets.
  4. Air bubbles.
  5. Pollin grains.
  6. Fecal contamination.
  7. Glass fragments.
Question 1: What are the most common crystals and renal calculi.
Show answer
Most common crystal are calcium oxalate or calcium phosphate.
Question :
Show answer
Question 2: What are the artifacts in the urine examination?
Show answer
There is starch, oil droplets, air bubbles, pollen grains and fecal contamination.
Question 3: What will be the pH for the bilirubin crystals??
Show answer
Bilirubin crystals form in acidic urine.

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