3-14. NORMAL CRYSTALS FOUND IN ACID URINE
It is important to be able to identify normal crystals found in urine so that one can recognize the presence of abnormal crystals.
Figure 3-18. Uric acid crystals.
a. Uric Acid Crystals (figire 3-18). Uric acid crystals are often found in acid specimens, particularly after standing for extended periods of time. If uric acid crystals are found in a fresh sample, a stone may be present in the renal system. These crystals can also be found in 16 percent of patients with gout. However, their presence does not necessarily indicate a pathological condition. Uric acid and its derivatives dissolve if the specimen is warmed. Uric acid crystals are found in many different forms and are greatly divergent in size and shape. They may take the form of prisms, plates, rosettes, and sheaves. They are yellow or reddish-brown in color, and may, like urates, impart a cloudy or milky appearance to the specimen. The yellow color of this crystal is its most characteristic attribute.
Figure 3-19. Amorphous urate crystals.
b. Amorphous Urate Crystals (figure 3-19). Amorphous urates appear as a granular precipitate having a brick-red color. Under the microscope, they can appear as fine yellowish granules, and at times they are almost colorless. They can be dissolved by treatment with alkali or by gentle heating of the urine. Amorphous urates are also dissolved by adding acetic acid or hydrochloric acid; after standing, they become colorless, rhombic uric acid crystals.
Figure 3-20. Calcium oxalate crystals.
c. Calcium Oxalate Crystals (figure 3-20). Calcium oxalate crystals are commonly found in acid urine but may also be seen in neutral or slightly alkaline specimens. They are usually not significant, and their presence is frequently the result of a diet rich in oxalic acid (for example, tomatoes, spinach, rhubarb, and asparagus). Calcium oxalate crystals vary greatly in size and shape but are generally seen as colorless, dodecahedral (12-sided) or octahedral (8-sided) crystals. They resemble small squares crossed by two intersecting diagonal lines giving them an "envelope" appearance. They may also appear as dumbbells or spheres and may tend to form urinary calculi. They are soluble in hydrochloric acid and not in acetic acid.
Figure 3-21. Sodium urate crystals.
d. Sodium Urate (figure 3-21). These crystals are usually fan-shaped and may be yellow in color.
Figure 3-22. Calcium sulfate crystals.
e. Calcium Sulfate (figure 3-22). These crystals, which are rarely observed, are colorless and assume the form of long needles or elongated prisms.
3-15. ABNORMAL CRYSTALS FOUND IN ACID URINE
Although small amounts of the chemicals from which "abnormal" crystals are derived occur normally in urine, the appearance of the substance in crystalline form is frequently of clinical significance.
Figure 3-23. Tyrosine/leucine crystals.
a. Leucine/Tyrosine (figure 3-23). Leucine and tyrosine crystals are cleaveage products of protein and usually occur simultaneously. They are not common and, if present in urine, usually indicate liver damage. Leucine crystals are yellowing, oily spheres often possessing radial and concentric striations. Tyrosine crystals appear black and resemble very fine needles arranged in sheaves with a constriction in the middle. Both leucine and tyrosine have been found following sulfonamide therapy. Leucine and tyrosine crystals may be differentiated to some degree by their different solubilities in the following substances:
- Hydrochloric acid Dilute acetic acid Alkali
- Leucine not soluble not soluble soluble
- Tyrosine soluble not soluble soluble
It should be noted that leucine, unlike tyrosine, is soluble in acetic acid if it is boiling. In addition, chemical tests exist to differentiate between the two crystals and confirm microscopic examination. First, albumin is removed from the specimen, which is evaporated to a small volume. One portion is fixed at pH 5.8 for leucine and another portion at pH 6.8--7.0 for tyrosine. These portions are placed in the refrigerator, and the tests are subsequently performed.
(1) Test for leucine. The crystals are dissolved in a little water and a drop of 10 percent copper sulfate is added. Leucine produces a blue color that remains after heating.
(2) Test for tyrosine. The crystalline precipitate is added to a few milliliters of Morner reagent. It is then heated to boiling. If the crystals are tyrosine, they will produce a green color. Morner reagent is composed of 1 part formalin, 45 parts water and 55 parts sulfuric acid.
Figure 3-24. Cystine crystals.
b. Cystine (fig. 3-24). Cystine is a breakdown product of protein which appears very rarely. The crystals occur in acid urine as colorless, highly refractile hexagonal plates with unequal sides. These crystals are not soluble in acetic acid, but they are soluble in hydrochloric acid or alkali. In cystinuria, an inborn metabolic error, the crystals appear very frequently. Cystine may be identified using a chemical test by the following procedure:
- STEP 1: Place an Acetest Tablet in a spot plate depression.
- STEP 2: Add 1 drop of 10 percent sodium cyanide in 1 mol/L sodium hydroxide to the tablet.
- STEP 3: Then add one drop of urine to the tablet.
- STEP 4: Observe the color of the solution around the tablet at 1 minute. A cherry-red color indicates more than 25 milligrams of cystine per 100 milliliters of sample.
Figure 3-25. Cholesterol crystals.
c. Cholesterol (figure 3-25). Cholesterol crystals are another form rarely found in urine. They appear in acid specimens as large, flat, transparent plates with abrupt edges and characteristic missing corners. They are quite soluble in chloroform and ether but are insoluble in alcohol. Cholesterol crystals often accompany chyluria, which results from an abdominal or thoracic obstruction to proper lymph drainage. These crystals may also appear in urine as a result of severe urinary tract infections or nephritis.
d. Sulfonamide Crystals. Following sulfonamide therapy, crystals of the drug, or a derivative, may be found in acid specimens. The sulfa compounds are more soluble in an alkaline pH and the maintenance of alkaline urine during drug administration may be required. The purpose of this alkalinity is to prevent crystallization of sulfa compounds in the kidney tubules with resulting damage. The various sulfa drugs have different crystalline forms that are often colored. A relatively simple way of identifying sulfa crystals is to dissolve the drug being administered in an alkaline solution, evaporate the solution almost to dryness, and compare the resulting crystals with those observed in the urine. Also to be included as an identifying test for sulfa crystals is the Hallay Test. Most sulfa compounds react with crude paper in the presence of acids, to form a yellow to orange color. Place 2 drops of urine on a blank strip of newspaper or paper towel. Add 1 drop of 25 percent hydrochloric acid. The immediate appearance of a yellow to orange color is positive for a sulfa compound.
| (1) Sulfanilamide (figure 3-26). These crystals are seen in the form of transparent bars or needles which may be grouped in sheaves. || |
Figure 3-26. Sulfanilamide crystals.
| (2) Sulfathiazole (figure 3-27). The form assumed by this crystal is a hexagonal plate or "shock of wheat" with central binding. || |
Figure 3-27. Sulfathiazole crystals.
| (3) Sulfadiazine (figure 3-28). These crystals are in the form of "shocks of wheat" with the binding toward one end, or they may resemble burrs. || |
Figure 3-28. Sulfadiazine Figure
| (4) Sulfaguanidine (figure 3-29). These crystals appear as either needles or plates. || |
3-29. Sulfaguanidine crystals. crystals.
| (5) Sulfapyridine (figure 3-30). Crystals of this drug resemble arrowheads or flower petals. || |
Figure 3-30. Sulfapyridine crystals.
3-16. CRYSTALS FOUND IN ALKALINE URINE
Amorphous phosphate, triple phosphate (ammonium magnesium phosphate), calcium phosphate, and ammonium urate crystals are frequently found in alkaline urine specimens. The phosphates are all soluble in acetic acid and may be differentiated from other crystals by this characteristic. They have no clinical significance unless present in large numbers and are always found in urine that has been standing for an extended period of time.
Figure 3-31. Amorphous phosphates crystals.
a. Amorphous Phosphates (figure 3-31). The amorphous phosphates are common in alkaline urine and appear as a granular white amorphous precipitate. They are soluble in acetic acid.
Figure 3-32. Triple phosphate crystals.
b. Triple Phosphate (figure 3-32). Triple phosphate crystals manifest a typical coffin lid shape with three, four, or six sides. The edges may frequently appear colored due to light diffraction. When they are artificially precipitated or rapidly deposited, they can assume feathery, leaf-like forms. In alkaline urine, they are occasionally seen as large, irregular, flat, granular plates that float on the surface and resemble iridescent scum. Although characteristically present in alkaline urine, triple phosphate crystals may also occur in neutral or slightly acid specimens. They dissolve in 100 percent acetic acid without effervescing. Triple phosphates may appear in the urine after the ingestion of fruits.
Figure 3-33. Calcium phosphate/dicalcium phosphate crystals.
c. Calcium Phosphate and Dicalcium Phosphate (figure 3-33). These crystals are usually found in alkaline urine and are deposited in several forms. Frequently calcium phosphate forms large, thin, granular, colorless plates. Dicalcium phosphate may appear as colorless prisms arranged in star or rosette patterns. The individual prisms are usually slender with one beveled, wedge-like end.
Figure 3-34. Ammonium urate crystals.
d. Ammonium Urates (figure 3-34). Ammonium urate crystals are precipitated when free ammonia is present as a result of bacterial action on long standing specimens. They are often seen when phosphates are present in the specimen. Ammonium urate crystals can be found in several different forms; they can appear as sheaves of fine needles, as dumbbells, and as "thorn apple" crystals, which are yellow, opaque, sphere-like bodies with irregular, spine-like projections. They can be dissolved by heating and by the addition of acetic acid, which, upon standing, results in the formation of colorless uric acid crystals.
Figure 3-35. Calcium carbonate crystals.
e. Calcium Carbonate (figure 3-35). Calcium carbonate crystals occur as amorphous granules or small, colorless spheres with a dumbbell shape. If 10 percent acetic acid is added to alkaline urine containing calcium carbonate crystals, they dissolve, and a gas is evolved as indicated by effervescence. This gas is CO2 (carbon dioxide).
3-17. EXTRANEOUS STRUCTURES
The presence in urine of extraneous materials, both organic and inorganic, can produce serious confusion and error in interpreting results. A number of circumstances can lead to contamination by foreign materials. Allowing urine to stand may result in such bacterial growth that the specimen becomes useless for analysis. Excessive exposure to air can cause confusing crystal formation. Unclean glassware frequently leads to contamination and subsequent misinterpretation; disposable containers should be used to avoid this problem. Contaminants may also be introduced from the lower urinary tract, from the external genitalia, and from fecal matter. Thus, great care should be taken while obtaining and preparing a specimen. A brief account is given of some of the common extraneous substances that may be present in urine.
a. Bacteria. Bacteria are not present in normal urine except as contaminants. Bacteria multiply rapidly and cause a uniform cloudiness throughout the sample. If they are found in a freshly voided specimen, urinary tract infection may be indicated. Large numbers of bacteria can give a positive test for protein.
b. Parasites. Parasites are sometimes found in urine. Animal parasites are relatively uncommon. Flagellates (such as Chilomastix mesnili and Trichomonas hominis), Schistosoma haematobium, and filaria are seen. One can also find the ova of intestinal parasites (for example, the ova of Enterobius vermicularis). Trichomonas vaginalis is by far the most common parasite present in urine.
Figure 3-36. Spermatozoa.
c. Spermatozoa (figure 3-36). Spermatozoa are easily identified by their characteristic shape and affinity for stains, especially methylene blue or Gram stain. They have no pathological significance and are reported only if the physician or pathologist has specifically requested a sperm report.
Figure 3-37. Yeast cells.
d. Yeast Cells (figure 3-37). Yeast cells resemble erythrocytes and leukocytes but usually show characteristic budding. They are nonnucleated and are insoluble in acetic acid. Yeast cells may be found in the sediment of a diabetic and of females but generally appear as contaminants. Their presence should be reported with some indication of the numbers present.
e. Foreign Elements Resembling Organized Sediments (Artifacts). The main sources of contamination are improperly cleaned specimen bottles and slides. A number of contaminants resemble blood cells and parasites, and may be mistaken for these structures. Scratched slides, glass chips, dirty eyepieces, and smudged objectives often cause confusion. It is wise to rotate the eyepiece periodically to be certain that extraneous structures, which may adhere to the eyepiece are not being identified as objects of significance contained in the specimen.
Figure 38. Starch granules.
(1) Starch granules (figure 3-38). These granules vary in shape and size. They turn blue-black upon the addition of iodine.
Figure 3-39. Oil droplets.
(2) Oil droplets (figure 3-39). Oil droplets are spherical and show concentric rings of light refraction upon focusing up and down with the fine adjustment. There is a wide variation in size.
Figure 3-40. Pollen granules.
(3) Pollen granules (figure 3-40). Pollen granules may be confused with erythrocytes or parasites. They vary in size and appearance according to their source. Those illustrated represent only a few of the many different types.
Figure 3-41. Diatoms.
(4) Diatoms (figure 3-41). Diatoms are one-celled plants which may be introduced into collecting bottles with tap water. Those illustrated here represent only a few of the many different types.
(5) Rotifers. Rotifers are unicellular animals with a pointed tail-like projection on one end. They appear in urine specimens when contaminated water is used to wash urine containers.
Figure 3-42. Hyphae of molds.
(6) Hyphae of molds (figure 3-42). The hyphae of molds are frequently mistaken for hyaline casts. The high degree of refraction of mold hyphae, the jointed or branching structures, and the accompanying spores should be looked for in order to identify them as mold hyphae.
Figure 3-43. Cloth fibers (cotton fibers).
(7) Cloth fibers (figure 3-43). Fibers of wool, cotton, silk, or other materials are sometimes mistaken for casts. One should become familiar with the appearance of such materials by suspending samples in water and examining them microscopically.