1 What is the clinical significance of crystalluria?

Crystalluria occurs when urine is saturated with crystallogenic substances. Various in vivo factors (e.g., urinary tract infection, diet) and several in vitro factors dictate whether crystal formation will occur. Factors that influence in vitro crystallogenesis include duration of sample storage, storage temperature, evaporation of water from the sample, urine pH, and the overgrowth of bacterial contaminants that may alter urine pH (e.g., urease-producing organisms).

To increase the likelihood that the crystals present in the urine sample represent those that may be present in the patient’s bladder, fresh urine samples should be analyzed within 1 hour of collection. Increased duration of storage time, especially when samples are refrigerated, significantly increases in vitro crystal formation. However, refrigeration is the method of choice to preserve the chemical and other sediment components of the urine sample. When crystalluria is detected in a refrigerated urine sample, it is prudent to verify the finding by prompt analysis of a freshly obtained sample.

The finding of crystalluria does not necessarily indicate the presence of uroliths or even a predisposition to form uroliths. A small amount of struvite or amorphous phosphate crystalluria can occur in clinically normal dogs and cats. Calcium carbonate crystalluria is a common finding in equine, goat, rabbit, and guinea pig urine samples. Detection of crystalluria may be diagnostically useful when abnormal crystal types are identified (e.g., ammonium urate, calcium oxalate monohydrate), when large aggregates of struvite or calcium oxalate crystals are found, or when crystalluria is observed in a patient that has confirmed urolithiasis. Evaluation of the type of crystals present may be useful to estimate the mineral component of the urolith(s) while awaiting results of complete urolith mineral analysis. However, the type of crystalluria present is not a definitive indicator of a urolith’s mineral content because uroliths are often heterogeneous. Additionally, sequential evaluation of crystalluria may aid in monitoring a patient’s response to therapy for urolith dissolution.

2 List crystals that form in acidic urine.

3 List crystals that form in neutral pH.

4 List crystals that form in alkaline urine.

5 What is the chemical composition of the crystal in Figure 29-1, and under what circumstances do these crystals occur?

Bilirubin may precipitate as orange to reddish brown granules or needlelike crystals. These crystals can be found in low numbers routinely in canine urine, especially in highly concentrated samples. When bilirubin crystals are found in other species or repeatedly in significant quantity in the urine of a canine patient, this suggests a disorder in bilirubin metabolism, which may be the result of a prehepatic (hemolysis), hepatic, or posthepatic disorder.

Figure 29-1 Bilirubin crystals in urine sediment from a dog with hepatic disease. These crystals appear as orange to reddish brown granules or needlelike crystals, often arranged in a “haystack” configuration. (Unstained; 125×.)

6 What is the common name and chemical composition of the crystal in Figure 29-2, and under what circumstances do these crystals occur?

Magnesium ammonium phosphate crystals are referred to as struvite crystals or “triple phosphate” crystals (a misnomer). These are colorless and frequently form variably sized, coffin lid–shaped crystals. However, struvite crystals can have a variable appearance and may occur as three- to eight-sided prisms, needles, or flat crystals with oblique ends (see Figure 29-2). They form most often in alkaline urine. Struvite crystalluria may form in vitro in refrigerated, stored urine samples or in those that become alkaline with storage. When struvite crystals are detected in a stored urine sample, the finding should be verified by examination of a freshly obtained urine sample.

Figure 29-2 Magnesium ammonium phosphate crystals (struvite) in urine sediment from a cat. These crystals are usually three-dimensional, variably sized, and rectangular in shape with oblique ends. (Unstained; 125×.)

Magnesium ammonium phosphate crystals are seen frequently in dogs and occasionally in cats. When found in significant number, struvite crystals are most often associated with bacterial infection by urease-producing bacteria, such as Staphylococcus or Proteus spp. In cats, however, they can occur in the absence of infection, likely due to ammonia excreted by the renal tubules. Struvite crystals may be seen in clinically normal animals that have alkaline urine, animals that have sterile or infection-associated uroliths of potentially mixed mineral composition, or those with urinary tract disease in the absence of urolithiasis.

7 What is the chemical composition of the crystal in Figure 29-3, and under what circumstances do these crystals occur?

Calcium oxalate dihydrate crystals occur as colorless, variably sized octahedrons that resemble an envelope or a Maltese cross. They form most often in acidic urine. Prolonged storage, especially with refrigeration, significantly increases the potential of in vitro calcium oxalate formation. A sample that becomes acidic during storage also may lead to in vitro calcium oxalate formation. When the crystals are detected in a stored urine sample, the finding should be verified by examination of a freshly obtained urine sample. These crystals may be seen in clinically normal animals, in those with calcium oxalate urolithiasis, with hypercalciuria, (e.g., due to corticosteroids), or with hyperoxaluria, (e.g., ingestion of vegetables high in oxalates, or infrequently with ethylene glycol toxicosis). Calcium oxalate dihydrate crystals have been reported with increased frequency in cats as a complication of urine acidification to manage struvite formation.

Figure 29-3 Calcium oxalate dihydrate crystals in urine sediment from a dog. Note the colorless, variably sized, octahedrons that, when viewed in a single plane, have the appearance of a square-shaped envelope. (Unstained; 125×.)

8 What is the chemical composition of the crystal in Figure 29-4, and under what circumstances do these crystals occur?

Calcium oxalate monohydrate crystals are colorless and variably sized. These crystals typically are flat with pointed ends and appear similar to hemp seeds or picket fence boards (see Figure 29-4). Less often, they may occur as spindle- or dumbbell-shaped crystals. Although either calcium oxalate monohydrate or dihydrate crystals can be seen with acute ethylene glycol toxicity, the monohydrate form is more diagnostic of intoxication, since this form is usually only seen during acute ethylene glycol toxicity and is rarely found in clinically normal animals. Formation of crystals is time dependent and occurs only during the early phase of intoxication. Crystalluria may be observed within 3 hours of ingestion in cats and within 6 hours in dogs and may last up to 18 hours after ingestion.

Figure 29-4 Calcium oxalate monohydrate crystals in urine sediment from a dog with acute ethylene glycol intoxication from ingestion of antifreeze. Note the long, rectangular, colorless, and variably sized crystals with pointed ends. These crystals are similar in appearance to magnesium ammonium phosphate crystals. However, unlike struvite, calcium oxalate monohydrate crystals are flat without the coffin lid–shaped, three-dimensional appearance. (Unstained; 125×.)

9 What serum biochemical information can also be used to support the diagnosis of ethylene glycol intoxication?

Ethylene glycol toxicosis is associated with signs of acute renal failure, including oliguria/anuria, marked azotemia, isosthenuria, hyperphosphatemia, hyperkalemia, hypocalcemia, and metabolic acidosis with greatly increased anion gap (40-50 mEq/L). Marked hyperglycemia (>350 mg/dl) may be observed in cats. The osmolal gap, which is calculated by subtracting the calculated serum osmolality from the actual measured serum osmolality, is normally 10 to 15 mOsm/kg. Values greater than 25 mOsm/kg suggest intoxication with osmotically active agents, such as ethylene glycol, mannitol, or ethanol. The formula for estimation of osmolality (expressed as mOsm/kg) follows:

10 What is the chemical composition of the crystal Figure 29-5, and under what circumstances do these crystals occur?

Calcium carbonate crystals occur individually or in clusters and are variably sized, yellow-brown or colorless, radiant spheres or dumbbell shaped. They usually form in alkaline urine and are seen in clinically normal horses, goats, rabbits, and guinea pigs. Calcium carbonate crystals have rarely been observed in dogs.

Figure 29-5 Calcium carbonate crystals in urine sediment from a normal horse. Note the variably sized, yellow-brown or colorless, radiant spheres and dumbbell shapes. (Unstained; 125×.)

11 What is the chemical composition of the crystal in Figure 29-6, and under what circumstances do these crystals occur?

Amorphous phosphates and urates have a similar shape and may occur as amorphous debris or small spheroids. Amorphous phosphates are distinguished from amorphous urates in two ways: phosphates are colorless and precipitate in alkaline urine, whereas urates are yellow-brown to black and precipitate in acidic urine. Amorphous phosphates are a common finding in alkaline urine of clinically normal animals. They are of no known diagnostic significance. However, amorphous urates are uncommon in clinically normal dogs and cats. They may be seen in animals with portovascular malformation, severe hepatic disease, or ammonium urate urolithiasis. Amorphous urates are often seen in Dalmatians and English bulldogs and may represent a predisposition to urate urolithiasis in these breeds. Dalmatians have defective purine metabolism and do not convert uric acid to allantoin. (Most other breeds convert uric acid to allantoin, which is water soluble and excreted in urine.) Additionally, Dalmatians may also have decreased tubular resorption of uric acid.

Figure 29-6 Amorphous urates in urine sediment from a Dalmatian dog. Amorphous phosphates and urates have a similar shape and may occur as amorphous debris or small spheroids. (Unstained; 125×.)

12 What is the chemical composition of the crystal in Figure 29-7, and under what circumstances do these crystals occur?

Ammonium urate crystals may also be referred to as ammonium biurate crystals. They are golden to brown and spherical with irregular protrusions, giving the appearance of a thorn apple or sarcoptic mange mites (see Figure 29-7). In cats, they may occur as smooth aggregates of spheroids. Ammonium urate crystals are seen in animals with portovascular malformation and with severe hepatic disease and infrequently in clinically normal Dalmatians and English bulldogs.

Figure 29-7 Ammonium urate crystals, also referred to as ammonium biurate crystals, in urine sediment from a dog with portocaval shunt. These crystals are golden to brown and spherical with irregular protrusions, suggesting a thorn apple or sarcoptic mange mites. (Unstained; 125×.)

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