Urinary Crystals

• Crystals frequently found in the urine are rarely of clinical significance. They may
appear as true geometrically formed structures or as amorphous material.

• The primary reason for the identification of urinary crystals is to detect the presence of
the relatively few abnormal types that may represent such disorders as liver disease,
inborn errors of metabolism, or renal damage caused by crystallization of
medications compounds within the tubules.

• Crystals are usually reported as rare, few, moderate, or many per hpf. Abnormal
crystals may be averaged and reported per lpf.

Crystal Formation

• Crystals are formed by the precipitation of urine solutes, including inorganic salts,
organic compounds, and medications (iatrogenic compounds).

• Precipitation is subject to changes in temperature, solute concentration, and pH,

which affect solubility.

• Solutes precipitate more readily at low temperatures. Therefore, the majority of

crystal formation takes place in specimens that have remained at room
temperature or been refrigerated prior to testing.

• Crystals are extremely abundant in refrigerated specimens and often present

problems because they obscure clinically significant sediment constituents.

• As the concentration of urinary solutes increases, their ability to remain in

solution decreases, resulting in crystal formation. The presence of crystals in
freshly voided urine is most frequently associated with concentrated (high
specific gravity) specimens.

• A valuable aid in the identification of crystals is the pH of the specimen because this
determines the type of chemicals precipitated.

 • In general, organic and iatrogenic compounds crystallize more easily in an acidic

pH, whereas inorganic salts are less soluble in neutral and alkaline solutions. An
exception is calcium oxalate, which precipitates in both acidic and neutral urine.

General Identification Techniques

• As discussed previously, the first consideration when identifying crystals is the urine
pH. In fact, crystals are routinely classified not only as normal and abnormal, but also
as to their appearance in acidic or alkaline urine. All abnormal crystals are found in
acidic urine.

• Additional aids in crystal identification include the use of polarized microscopy and
solubility characteristics of the crystals.

• The geometric shape of a crystal determines its birefringence and, therefore, its
ability to polarize light.

• Amorphous urates that frequently form in refrigerated specimens and obscure

sediments may dissolve if the specimen is warmed.

• Amorphous phosphates require acetic acid to dissolve, and this is not practical,
as formed elements, such as RBCs, will also be destroyed.

• When solubility characteristics are needed for identification, the sediment should
be aliquoted to prevent destruction of other elements.

• The most common crystals seen in acidic urine are urates, consis ng of amorphous urates,
uric acid, acid urates, and sodium urates.

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 NORMAL CRYSTALS SEEN IN ACIDIC URINE

AMORPHOUS URATES

• Microscopically, most urates crystals appear yellow to reddish brown and are the only
normal crystals found in acidic urine that appear colored.

• Amorphous urates appear microscopically as yellow-brown granules.

• They may occur in clumps resembling granular casts and a ached to other sediment
structures.

• Amorphous urates are frequently encountered in specimens that have been

refrigerated and produce a very characteris c pink sediment.

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 o Accumula on of the pigment, uroerythrin, on the surface of the granules is the

cause of the pink color.

• Amorphous urates are found in acidic urine with a pH greater than 5.5, whereas uric acid
crystals can appear when the pH is lower.

URIC ACIDS

• Uric acid crystals are seen in a variety of shapes, including rhombic, four-sided at plates
(whetstones), wedges, and rose es.

• They usually appear yellow-brown, but may be colorless and have a six-sided shape, similar
to cys ne crystals (Figs. 6–76 and 6–77).

• Uric acid crystals are highly birefringent under polarized light, which aids in dis nguishing
them from cys ne crystals (Fig. 6–78 A and B).

• Increased amounts of uric acid crystals, par cularly in fresh urine, are associated with
increased levels of purines and nucleic acids and are seen in pa ents with leukemia who are
receiving chemotherapy, in pa ents with Lesch-Nyhan syndrome and some mes in pa ents
with gout.
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 ACID URATES & SODIUM URATES

• They are frequently seen in conjunc on with amorphous urates and have li le clinical
signi cance.

• Acid urates appear as larger granules and may have spicules similar to the ammonium biurate
crystals seen in alkaline urine.

• Sodium urate crystals are needle-shaped and are seen in synovial uid during episodes of
gout, but may also appear in the urine.

CALCIUM OXALATES

• Calcium oxalate crystals are frequently seen in acidic urine, but they can be found in neutral
urine and even rarely in alkaline urine.

• The most common form of calcium oxalate crystals is the dihydrate that is easily recognized
as a colorless, octahedral envelope or as two pyramids joined at their bases (Figs. 6–79, 6–
80, and 6–81).

• Less characteris c and less frequently seen is the monohydrate form (Fig. 6–82).
Monohydrate calcium oxalate crystals are oval or dumbbell shaped.

• Both the dihydrate and monohydrate forms are birefringent under polarized light.

• This may be helpful to dis nguish the monohydrate form from non-polarizing RBCs.

• The nding of clumps of calcium oxalate crystals in fresh urine may be related to the
forma on of renal calculi, because the majority of renal calculi are composed of calcium
oxalate.
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• They are also associated with foods high in oxalic acid, such as tomatoes and asparagus, and
ascorbic acid, because oxalic acid is an end product of ascorbic acid metabolism.

• The primary pathologic signi cance of calcium oxalate crystals is the very no ceable presence
of the monohydrate form in cases of ethylene glycol (an freeze) poisoning.

• The monohydrate form is most frequently seen in children and pets because an freeze
tastes sweet and uncovered containers le in the garage can be very temp ng! Massive
amounts of crystals are frequently produced in these cases.

NORMAL CRYSTALS SEEN IN ALKALINE URINE

AMORPHOUS PHOSPHATES

• Amorphous phosphates are granular in appearance, similar to amorphous urates

(Figs. 6–83 and 6–84).

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• When present in large quantities following specimen refrigeration, they cause a white
precipitate that does not dissolve on warming. They can be differentiated from
amorphous urates by the color of the sediment and the urine pH.

TRIPLE PHOSPHATE (AMMONIUM MAGNESIUM PHOSPHATE)

• Triple phosphate (ammonium magnesium phosphate) crystals are commonly seen in

alkaline urine.

• In their routine form, they are easily identified by their prism shape that frequently
resembles a “coffin lid” (Figs. 6–85 and 6–86).

• As they disintegrate, the crystals may develop a feathery appearance. Triple

phosphate crystals are birefringent under polarized light.

• They have no clinical significance; however, they are often seen in highly alkaline
urine associated with the presence of urea-splitting bacteria.

 CALCIUM PHOSPHATE CRYSTALS

• Calcium phosphate crystals are not frequently encountered.

• They may appear as colorless, at rectangular plates or thin prisms o en in rose e

forma ons.

• The rose e forms may be confused with sulfonamide crystals when the urine pH is in
the neutral range.

• Calcium phosphate crystals dissolve in dilute ace c acid and sulfonamides do not.

• They have no clin ical signi cance, although calcium phosphate is a common cons tuent of
renal calculi.

CALCIUM CARBONATE CRYSTALS

• Calcium carbonate crystals are small and colorless, with dumbbell or spherical shapes (Fig. 6–
87).

• They may occur in clumps that resemble amorphous material, but they can be dis nguished
by the forma on of gas a er the addi on of ace c acid.

• They are also birefringent, which di eren ates them from bacteria. Calcium carbonate
crystals have no clinical signi cance.

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 AMMONIUM BIURATE CRYSTALS

• Ammonium biurate crystals exhibit the characteris c yellow-brown color of the urate crystals
seen in acidic urine.

• They are frequently described as “thorny apples” because of their appearance as spicule-
covered spheres (Fig. 6–88).

• Except for their occurrence in alkaline urine, ammonium biurate crystals resemble other
urates in that they dissolve at 60°C and convert to uric acid crystals when glacial ace c acid is
added.

• Ammonium biurate crystals are almost always encountered in old specimens and may be
associated with the presence of the ammonia produced by urea-spli ng bacteria (Figs. 6–89
A and B and 6–90).

ABNORMAL URINE CRYSTALS

• Abnormal urine crystals are found in acidic urine or rarely in neutral urine.

• Most abnormal crystals have very characteris c shapes. However, their iden ty can be
con rmed by pa ent informa on, including disorders and medica on.
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 CYSTINE CRYSTALS

• Cys ne crystals are found in the urine of persons who inherit a metabolic disorder that
prevents reabsorp on of cys ne by the renal tubules (cys nuria).

• Persons with cys nuria have a tendency to form renal calculi, par cularly at an early
age.

• Cys ne crystals appear as colorless, hexagonal plates and may be thick or thin (Figs. 6–91
and 6–92).

• Disintegra ng forms may be seen in the presence of ammonia.

• They may be di cult to di eren ate from colorless uric acid crystals.
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 • Uric acid crystals are very birefringent under polarized microscopy, whereas only thick
cys ne crystals have polarizing capability.

• Posi ve con rma on of cys ne crystals is made using the cyanide-nitroprusside test.

CHOLESTEROL CRYSTALS

• Cholesterol crystals are rarely seen unless specimens have been refrigerated, because the
lipids remain in droplet form.

• However, when observed, they have a most characteris c appearance, resembling a

rectangular plate with a notch in one or more corners (Fig. 6–93).

• They are associated with disorders producing lipiduria, such as the nephro c syndrome, and
are seen in conjunc on with fa y casts and oval fat bodies.

• Cholesterol crystals are highly birefringent with polarized light (Fig. 6–94).
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 RADIOGRAPHIC DYE CRYSTALS

• Crystals of radiographic contrast media have a very similar appearance to cholesterol crystals
and also are highly birefringent.

• Di eren a on is best made by comparison of the other urinalysis results and the pa ent
history.

• As men oned previously, cholesterol crystals should be accompanied by other lipid

elements and heavy proteinuria.

• Likewise, the speci c gravity of a specimen containing radiographic contrast media is

markedly elevated when measured by refractometer.

CRYSTALS ASSOCIATED WITH LIVER DISORDERS

In the presence of severe liver disorders, three rarely seen crystals may be found in the urine
sediment. They are crystals of tyrosine, leucine, and bilirubin.

TYROSINE CRYSTALS

• Tyrosine crystals appear as ne colorless to yellow needles that frequently form clumps or
rose es (Figs. 6–95 and 6–96).

• They are usually seen in conjunc on with leucine crystals in specimens with posi ve
chemical test results for bilirubin.

• Tyrosine crystals may also be encountered in inherited disorders of amino acid metabolism.
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 LEUCINE CRYSTALS

• Leucine crystals are yellow-brown spheres that demonstrate concentric circles and radial
stria ons (Fig. 6–97).

• They are seen less frequently than tyrosine crystals and, when present, should be
accompanied by tyrosine crystals.

BILIRUBIN CRYSTALS

• Bilirubin crystals are present in hepa c disorders producing large amounts of bilirubin in the
urine.

• They appear as clumped needles or granules with the characteris c yellow color of bilirubin
(Fig. 6–98). A posi ve chemical test result for bilirubin would be expected.

• In disorders that produce renal tubular damage, such as viral hepa s, bilirubin crystals may
be found incorporated into the matrix of casts.
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 SULFONAMIDE CRYSTALS

• Prior to the development of more soluble sulfonamides, the nding of these crystals in the
urine of pa ents being treated for UTIs was common.

• Inadequate pa ent hydra on was and s ll is the primary cause of sulfonamide

crystalliza on.

• The appearance of sulfonamide crystals in fresh urine can suggest the possibility of tubular
damage if crystals are forming in the nephron.

• A variety of sulfonamide medica ons are currently on the market; therefore, one can expect
to encounter a variety of crystal shapes and colors.

• Shapes most frequently encountered include needles, rhombics, whetstones, sheaves of

wheat, and rose es with colors ranging from colorless to yellow-brown (Figs. 6–99 and 6–
100). A check of the pa ent’s medica on history aids in the iden ca on con rma on.

AMPICILLIN CRYSTALS

• Precipita on of an bio cs is not frequently encountered except for the rare observa on of
ampicillin crystals following massive doses of this penicillin compound without adequate
hydra on.

• Ampicillin crystals appear as colorless needles that tend to form bundles following
refrigera on (Fig. 6–101 A and B). Knowledge of the pa ent’s history can aid in the
iden ca on.
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 URINARY SEDIMENT ARTIFACTS

• Contaminants of all types can be found in urine, par cularly in specimens collected under
improper condi ons or in dirty containers.

• The most frequently encountered ar facts include starch, oil droplets, air bubbles, pollen
grains, bers, and fecal contamina on.

• Because ar facts frequently resemble pathologic elements such as RBCs and casts, ar facts
can present a major problem to students.

• They are o en very highly refrac le or occur in a di erent microscopic plane than the true
sediment cons tuents. The repor ng of ar facts is not necessary.

STARCH GRANULES

• Starch granule contamina on may occur when cornstarch is the powder used in powdered
gloves.

• The granules are highly refrac le spheres, usually with a dimpled center (Fig. 6–102).

• They resemble fat droplets when polarized, producing a Maltese cross forma on.

• Starch granules may also occasionally be confused with RBCs.

• Di eren a on between starch and pathologic elements can be made by considering other
urinalysis results, including chemical tests for blood or protein and the presence of oval fat
bodies or fa y casts.
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 OIL DROPLETS & AIR BUBBLES

• Oil droplets and air bubbles also are highly refrac le and may resemble RBCs to
inexperienced laboratory personnel.

• Oil droplets may result from contamina on by immersion oil or lo ons and creams and
maybe seen with fecal contamina on (Fig. 6–103).

• Air bubbles occur when the specimen is placed under a cover slip. The presence of these
ar facts should be considered in the context of the other urinalysis results.

POLLEN GRAINS

• Pollen grains are seasonal contaminants that appear as spheres with a cell wall and
occasional concentric circles (Fig. 6–104).

• Like many ar facts, their large size may cause them to be out of focus with true sediment
cons tuents.
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 HAIR AND FIBERS

• Hair and bers from clothing and diapers may ini ally be mistaken for casts (Figs. 6–105 and
6–106), though they are usually much longer and more refrac le.

• Examina on under polarized light can frequently di eren ate between bers and casts (Fig.
6–107). Fibers o en polarize, whereas casts, other than fa y casts, do not polarize.

VEGETABLE FIBER

• Improperly collected specimens or rarely the presence of a stula between the intes nal and
urinary tracts may produce fecal specimen contamina on.

• Fecal ar facts may appear as plant and meat bers or as brown amorphous material in a
variety of sizes and shapes (Fig. 6–108).
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