URINARY CRYSTALS. by Geoffrey K. Dube and Robert S. Brown

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1 URINARY CRYSTALS by Geoffrey K. Dube and Robert S. Brown A 26 year-old man presents with a fever and weakness. His WBC is 133,000, with 83% blasts. Creatinine is 2.0 mg/dl and serum uric acid is 15.4 mg/dl. 2004, Beth Israel Deaconess Medical Center, Inc.

2 A 26 year-old man presents with fever and a rash. His WBC is 133,000, with 83% blasts. Creatinine is 2.0 mg/dl and serum uric acid is 15.4 mg/dl. Assuming that this patient has uric acid crystalluria, which of the following might you find on urine dipstick? a. Urine ph 5.0 b. 4+ heme c. 4+ glucose d. 4+ protein

3 Uric acid crystals invariably form in acidic urine, typically with a urine ph < 5.5. Uric acid is soluble in alkaline urine, preventing the precipitation of urate crystals. The inability of uric acid to crystallize at urine ph > 7.0 is the rationale for urinary alkalinization in patients at risk for acute uric acid nephropathy. Uric acid crystalluria is not associated with significant amounts of hematuria, glycosuria or proteinuria.

4 Although crystals can be seen in certain clinical scenarios, such as kidney stone disease or acute crystal nephropathy, visualizing crystals under the microscope does not guarantee that the crystals were present in the urinary system. Crystals can continue to form after micturition. Crystal precipitation after micturition is most commonly due to changes in temperature, as can occur if the urine is stored at room temperature or in a refrigerator, or changes in urinary ph, as can occur in the presence of infection due to urea-splitting organisms.

5 Assuming that this patient has uric acid crystals, what would you expect to see on microscopy? a. Amber-colored rhomboid crystals b. Colorless, hexagonal crystals c. Colorless, "coffin-lid"-shaped crystals d. Colorless, dumbbell-shaped crystals e. "Shocks of wheat"

6 Uric acid crystals can vary in both size and shape, as can be seen in the slide above. They can look like barrels, rosettes, rhomboids, needles or hexagonal plates. They are usually amber in color, irrespective of the size or shape of the individual crystal. However, urate crystals may assume the color of any pigments (such as bilirubin or the medication pyridium) that are present in the urine. Urate crystals can occasionally be seen in normal subjects, although they are much more common in patients with urate nephrolithiasis or acute urate nephropathy.

7 The slide on the left shows a a uric acid crystal as viewed with light microscopy. The slide on the right shows the same crystal as viewed under polarized light. Uric acid crystals are birefringent and beneath polarized light assume a polychromatic appearance. Their bright colors under polarized light distinguishes uric acid crystals from other types of crystals.

8 In contrast to polymorphic urate crystals, cystine crystals are monomorphic, colorless hexagonal plates which look similar to benzene rings. The urine sediments from two patients with cystine crystals are shown above. Cystine crystals may be isolated or may be heaped upon one another. They occur in the sediment of patients with cystinuria, a genetic defect in renal cystine transport. They are found in acidic urine, typically with a urine ph < 6.0.

9 Triple phosphate, or struvite, crystals are described as having a "coffin-lid"-shaped appearance. Several struvite crystals are shown above. Struvite crystals are composed of magnesium ammonium phosphate. They are typically seen in alkaline urine, with a urine ph > 7.0.

10 Triple phosphate crystals are seen in patients with urinary tract infections caused by urea-splitting bacteria, such as Proteus mirabilis, and are frequently found in the urine of patients with infected calculi (struvite stones). In addition to triple phosphate crystals, microscopy in these patients with urinary tract infections may show significant leukocyturia (arrows, above right) and bacteriuria.

11 Calcium oxalate crystals are usually found in acidic urine. They may occur as either bihydrated or monohydrated calcium oxalate. Calcium oxalate bihydrate crystals appear as colorless bipyramids of various sizes ( envelope form, above left). Calcium oxalate monohydrate crystals are colorless and can assume several shapes, including ovoids, biconcave disks, rods and dumbbells (above right, yellow arrows). They can be seen in normal individuals with high dietary oxalate ingestion, in patients with nephrolithiasis, and in patients with acute renal failure due to ethylene glycol ingestion. Above right, reprinted with permission, Coe F.L. et al.. New Engl J Med 327:

12 Urinary crystals can also be seen in patients taking certain medications. One example is sulfadiazine: these crystals appear as striated shells or "shocks of wheat. A sulfadiazine crystal is shown on the left. Other medications that can cause urine crystals to form include indinavir, intravenous acyclovir, and triamterene. When these medications are given in high doses or to volume depleted patients, the crystals can cause acute renal failure by crystalline blockage of the renal tubules. An example of an indinavir crystal is shown on the right: the top panel shows rectangular plates of various sizes containing needle crystals, while the bottom panel shows indinavir crystals in a sheaf of numerous, densely packed needles. Indinavir crystals reprinted with permission, Gagnon, R. F. et. al. Ann Intern Med 1998;128:321

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