Urinalysis and Body Fluids Strasinger 7th Ed PDF - Microscopic Urine Exam

Chapter 7 | Microscopic Examination of Urine 199 All types of casts may occur in the broad form. However, considering the accompanying urinary stasis, the broad casts seen most commonly are granular and waxy (Figs. 7-69 and 7-70 A and B). Broad, waxy casts that are bile stained are seen as the...

Chapter 7 | Microscopic Examination of Urine 199 All types of casts may occur in the broad form. However, considering the accompanying urinary stasis, the broad casts seen most commonly are granular and waxy (Figs. 7-69 and 7-70 A and B). Broad, waxy casts that are bile stained are seen as the result of tubular necrosis caused by viral hepatitis (Fig. 7-71). Figure 7–71 Broad bile-stained waxy cast (×400). Urinary Crystals Crystals frequently found in the urine are rarely of clinical sig- nificance. They may appear as true geometrically formed struc- tures or as amorphous material. The primary reason for the identification of urinary crystals is to detect the presence of the Figure 7–69 KOVA-stained broad waxy cast (×400). relatively few abnormal types that may represent such disor- ders as liver disease, inborn errors of metabolism, or renal damage caused by crystallization of medication compounds within the tubules. Usually crystals are 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, in- cluding 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 have been refrigerated before testing. Crystals are extremely abun- dant in refrigerated specimens and often present problems because they obscure sediment constituents that are clinically A significant. 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 associated most frequently 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 excep- tion is calcium oxalate, which precipitates in both acidic and neutral urine. B Technical Tip 7-19. The most valuable initial aid for Figure 7–70 A. Broad granular cast. B. Broad granular cast becom- identifying crystals in a urine specimen is the pH. ing waxy (×400). 200 Part Two | Urinalysis SUMMARY 7-5 Urine Casts Complete Sources of Urinalysis Clinical Appearance Error Reporting Correlations Significance Hyaline Colorless, Mucus, fibers, Average number Protein Glomerulonephritis homogenous hair, per lpf Blood (exercise) Pyelonephritis matrix increased Color (exercise) Chronic renal disease lighting Congestive heart failure Stress and exercise RBC Orange-red color, RBC clumps Average number RBCs Glomerulonephritis cast matrix per lpf Blood Strenuous exercise containing Protein RBCs WBC Cast matrix con- WBC clumps Average number WBCs Pyelonephritis taining WBCs per lpf Protein AIN LE Bacterial Bacilli bound to Granular casts Average number WBC casts Pyelonephritis protein matrix per lpf (pyelonephritis) WBCs LE Nitrite Protein Bacteria Epithelial RTE cells attached WBC cast Average number Protein Renal tubular damage Cell to protein per lpf RTE cells matrix Granular Coarse and fine Clumps of Average number Protein Glomerulonephritis granules in a small per lpf Cellular casts Pyelonephritis cast matrix crystals RBCs Stress and exercise Columnar RTE WBCs cells Waxy Highly refractile Fibers and Average number Protein Stasis of urine flow cast with fecal per lpf Cellular casts Chronic renal failure jagged ends material Granular casts and notches WBCs RBCs Fatty Fat droplets and Fecal debris Average number Protein Nephrotic syndrome oval fat bodies per lpf Free fat droplets Toxic tubular necrosis attached to Oval fat bodies Diabetes mellitus protein matrix Crush injuries Broad Wider-than- Fecal material, Average number Protein Extreme urine stasis normal cast fibers per lpf WBCs Renal failure matrix RBCs Granular casts Waxy casts  Chapter 7 | Microscopic Examination of Urine 201 General Identification Techniques Knowledge of these solubility characteristics can be used to aid in identification. Amorphous urates that frequently form in re- The crystals seen most commonly have very characteristic frigerated specimens and obscure sediments may dissolve if the shapes and colors; however, variations do occur and can pres- specimen is warmed. Amorphous phosphates require acetic acid ent identification problems, particularly when they resemble to dissolve, and this is not practical, as formed elements, such as abnormal crystals. As discussed previously, the first consider- RBCs, also will be destroyed. When solubility characteristics are ation when identifying crystals is the urine pH. In fact, crystals needed for identification, the sediment should be aliquoted to are routinely classified not only as normal and abnormal but prevent destruction of other elements. In Table 7-6, characteris- also as to their appearance in acidic or alkaline urine. All tics for the crystals encountered most commonly are provided. abnormal crystals are found in acidic urine. Another aid in crystal identification is the use of polarized Normal Crystals Seen in Acidic Urine microscopy. The geometric shape of a crystal determines its birefringence and, therefore, its ability to polarize light. Al- The most common crystals seen in acidic urine are urates, con- though the size of a particular crystal may vary (slower crys- sisting of amorphous urates, uric acid, acid urates, and sodium tallization produces larger crystals), the basic structure remains urates. Microscopically, most urate crystals appear yellow to the same. Therefore, polarization characteristics for a particular reddish brown and are the only normal crystals found in acidic crystal are constant for identification purposes. urine that appear colored. Just as changes in temperature and pH contribute to crystal Amorphous urates appear microscopically as yellow- formation, reversal of these changes can cause crystals to dissolve. brown granules (Fig. 7-72). They may occur in clumps Table 7–6 Major Characteristics of Normal Urinary Crystals Crystal pH Color Appearance Uric acid Acid Yellow-brown (rosettes, wedges) Amorphous urates Acid Brick dust or yellow brown Sodium urates Acid Colorless Calcium oxalate Acid/neutral (alkaline) Colorless (envelopes, oval, dumbbell) Amorphous phosphates Alkaline/neutral White–colorless Continued 202 Part Two | Urinalysis Table 7–6 Major Characteristics of Normal Urinary Crystals—cont’d Crystal pH Color Appearance Calcium phosphate Alkaline/neutral Colorless Triple phosphate Alkaline Colorless (“coffin lids”) Ammonium biurate Alkaline Yellow-brown (“thorny apples”) Calcium carbonate Alkaline Colorless (dumbbells) Figure 7–72 Amorphous urates (×400). resembling granular casts and attached to other sediment structures (Fig.7-73). Amorphous urates are encountered fre- Figure 7–73 Amorphous urates attached to a fiber. quently in specimens that have been refrigerated but disappear when the urine is warmed. They produce a very characteristic pink sediment caused by accumulation of the pigment uroery- (Figs. 7-74 and 7-75). Uric acid crystals are highly birefringent thrin on the surface of the granules. Amorphous urates are under polarized light, which aids in distinguishing them from found in acidic urine with a pH greater than 5.5, whereas uric cystine crystals (Fig. 7-76 A and B). Increased amounts of uric acid crystals can appear when the pH is lower. acid crystals, particularly in fresh urine, are associated with Uric acid crystals are seen in a variety of shapes, including increased levels of purines and nucleic acids and are seen in rhombic, four-sided flat plates (whetstones), wedges, and patients with leukemia who are receiving chemotherapy, in rosettes. They usually appear yellow-brown but may be col- patients with Lesch-Nyhan syndrome (see Chapter 9), and orless and have a six-sided shape, similar to cystine crystals sometimes in patients with gout.  Chapter 7 | Microscopic Examination of Urine 203 A Figure 7–74 Uric acid crystals (×400). B Figure 7–76 A. Uric acid crystals under polarized light (×100). B. Uric acid crystals under polarized light (×400). Figure 7–75 Clump of uric acid crystals (×400). Notice the whet- stone, not hexagonal, shape that differentiates uric acid crystals from cystine crystals. Acid urates and sodium urates are rarely encountered and, like amorphous urates, are seen in urine that is less acidic. Fre- quently they are seen in conjunction with amorphous urates and have little clinical significance. Acid urates appear as larger granules and may have spicules similar to the ammonium bi- urate crystals seen in alkaline urine. Sodium urate crystals are needle shaped and are seen in synovial fluid during episodes of gout, but they also may appear in the urine (Fig. 7-77). Calcium oxalate crystals are seen frequently 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, Figure 7–77 Sodium urate crystals. octahedral envelope or as two pyramids joined at their bases (Figs. 7-78, 7-79, and 7-80). Less characteristic and less fre- quently seen is the monohydrate form (Fig. 7-81). Monohy- The finding of clumps of calcium oxalate crystals in fresh drate calcium oxalate crystals are oval or dumbbell shaped. urine may be related to the formation of renal calculi because Both the dihydrate and monohydrate forms are birefringent the majority of renal calculi are composed of calcium oxalate. under polarized light. This may be helpful to distinguish the Also, they are associated with foods high in oxalic acid, such monohydrate form from nonpolarizing RBCs. Sometimes cal- as tomatoes and asparagus, and ascorbic acid because oxalic cium oxalate crystals are seen in clumps attached to mucous acid is an end product of ascorbic acid metabolism. The pri- strands and may resemble casts. mary pathological significance of calcium oxalate crystals is the 204 Part Two | Urinalysis Figure 7–81 Monohydrate calcium oxalate crystals (×400). Figure 7–78 Classic dihydrate calcium oxalate crystals (×400). very noticeable presence of the monohydrate form in cases of ethylene glycol (antifreeze) poisoning. The monohydrate form is seen most frequently in children and pets because antifreeze tastes sweet and uncovered containers left in the garage can be very tempting! Massive amounts of crystals are frequently produced in these cases. Normal Crystals Seen in Alkaline Urine Phosphates represent the majority of the crystals seen in alkaline urine and include amorphous phosphate, triple phosphate, and calcium phosphate. Other normal crystals associated with al- kaline urine are calcium carbonate and ammonium biurate. Amorphous phosphates are granular in appearance, similar to amorphous urates (Figs. 7-82 and 7-83). When present in large quantities after specimen refrigeration, they cause a white pre- cipitate that does not dissolve on warming. They can be differ- Figure 7–79 Classic dihydrate calcium oxalate crystals under phase entiated from amorphous urates by the color of the sediment microscopy (×400). and the urine pH. Triple phosphate (ammonium magnesium phosphate) crystals are seen commonly in alkaline urine. In their routine form, they are identified easily by their prism shape that fre- quently resembles a “coffin lid” (Figs. 7-84 A and B and 7-85). As they disintegrate, the crystals may develop a feathery appearance. Triple phosphate crystals are birefringent under Figure 7–80 Attached classic dihydrate calcium oxalate crystals (×400). Figure 7–82 Amorphous phosphates (×400). Urine pH 7.0.  Chapter 7 | Microscopic Examination of Urine 205 Figure 7–85 Triple phosphate crystals (arrow) and amorphous phosphates (×400). Figure 7–83 Amorphous phosphates (×400). or thin prisms often in rosette formations. The rosette forms may be confused with sulfonamide crystals when the urine pH is in the neutral range. Calcium phosphate crystals dissolve in dilute acetic acid, but sulfonamides do not. They have no clin- ical significance, although calcium phosphate is a common constituent of renal calculi. Calcium carbonate crystals are small and colorless, with dumbbell or spherical shapes (Fig. 7-86). They may occur in clumps that resemble amorphous material, but they can be dis- tinguished by the formation of gas after the addition of acetic acid. They are also birefringent, which differentiates them from bacteria. Calcium carbonate crystals have no clinical significance. Ammonium biurate crystals exhibit the characteristic yellow-brown color of the urate crystals seen in acidic urine. A Frequently they are described as “thorny apples” because of their appearance as spicule-covered spheres (Fig. 7-87). Except for their occurrence in alkaline urine, ammonium biurate crys- tals resemble other urates in that they dissolve at 60°C and convert to uric acid crystals when glacial acetic 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-splitting bacteria (Figs. 7-88 A and B and 7-89). B Figure 7–84 A. Triple phosphate crystal using bright-field mi- croscopy (×400). B. Triple phosphate under polarized light. polarized light. They have no clinical significance; however, they are seen often in highly alkaline urine associated with the presence of urea-splitting bacteria. Calcium phosphate crystals are not encountered fre- quently. They may appear as colorless, flat rectangular plates Figure 7–86 Calcium carbonate crystals (×400). 206 Part Two | Urinalysis Figure 7–87 Ammonium biurate crystals (×400). Notice the “thorny apple” appearance. (Courtesy of Kenneth L. McCoy, MD.) Figure 7–89 Ammonium biurate crystals (×400). Note thorns (arrow). Abnormal Urine Crystals Abnormal urine crystals are found in acidic urine or, rarely, in neutral urine. Most abnormal crystals have very characteristic shapes. However, their identity can be confirmed by patient information, including disorders and medications (Table 7-7). Iatrogenic crystals can be caused by a variety of compounds, particularly when they are administered in high concentra- tions. They may be of clinical significance when they precipi- A tate in the renal tubules. The iatrogenic crystals that are encountered most commonly are discussed in this section. Cystine Crystals Cystine crystals are found in the urine of people who inherit a metabolic disorder that prevents reabsorption of cystine by the renal tubules (cystinuria). People with cystinuria tend to form renal calculi, particularly at an early age. Cystine crystals appear as colorless, hexagonal plates and Triple may be thick or thin (Figs. 7-90 and 7-91). Disintegrating phosphate crystal forms may be seen in the presence of ammonia. They may be difficult to differentiate from colorless uric acid crystals. Uric acid crystals are very birefringent under polarized microscopy, whereas only thick cystine crystals have polarizing capability. Positive confirmation of cystine crystals is made using the cyanide–nitroprusside test (see Chapter 9). B Cholesterol Crystals Cholesterol crystals are rarely seen unless specimens have been Figure 7–88 A. Ammonium biurate and triple phosphate crystals refrigerated because the lipids remain in droplet form. How- (×100). Note thorn (arrow). B. Ammonium biurate and triple phos- ever, when observed, they have a most characteristic appear- phate crystals (×400). ance, resembling a rectangular plate with a notch in one or more corners (Fig. 7-92). They are associated with disorders producing lipiduria, such as nephrotic syndrome, and are seen in conjunction with fatty casts and oval fat bodies. Cholesterol crystals are highly birefringent with polarized light (Fig. 7-93).  Chapter 7 | Microscopic Examination of Urine 207 Table 7–7 Major Characteristics of Abnormal Urinary Crystals Crystal pH Color/Form Disorders Appearance Cystine Acid Colorless (hexagonal Inherited cystinuria plates) Cholesterol Acid Colorless (notched plates) Nephrotic syndrome Leucine Acid/neutral Yellow (concentric circles) Liver disease Tyrosine Acid/neutral Colorless–yellow (needles) Liver disease Bilirubin Acid Yellow Liver disease Sulfonamides Acid/neutral Varied Infection treatment Radiographic dye Acid Colorless (flat plates) Radiographic procedure Ampicillin Acid/neutral Colorless (needles) Infection treatment Radiographic Dye Crystals Crystals Associated With Liver Disorders Crystals of radiographic contrast media appear similar to cho- In the presence of severe liver disorders, three crystals that usu- lesterol crystals and also are highly birefringent. ally are rarely seen may be found in the urine sediment. They Differentiation is best made by comparison of the results are crystals of tyrosine, leucine, and bilirubin. of the other urinalysis, as well as the patient history. As Tyrosine crystals appear as fine colorless to yellow needles mentioned previously, cholesterol crystals should be accompa- that frequently form clumps or rosettes (Figs. 7-94 and 7-95). nied by other lipid elements and heavy proteinuria. Likewise, Usually they are seen in conjunction with leucine crystals in the specific gravity of a specimen containing radiographic specimens with positive chemical test results for bilirubin. Ty- contrast media is markedly elevated when measured by rosine crystals also may be encountered in inherited disorders refractometer. of amino acid metabolism (see Chapter 9). 208 Part Two | Urinalysis Figure 7–90 Cystine crystals (×400). Figure 7–93 Cholesterol crystals under polarized light (×400). Figure 7–91 Clump of cystine crystals (×400). Notice the hexagonal Figure 7–94 Tyrosine crystals in fine needle clumps (×400). shape still visible. Figure 7–95 Tyrosine crystals in rosette forms (×400). Figure 7–92 Cholesterol crystals. Notice the notched corners (×400). yellow color of bilirubin (Fig. 7-97 A and B). A positive chemical test result for bilirubin would be expected. In disorders that pro- Leucine crystals are yellow-brown spheres that demon- duce renal tubular damage, such as viral hepatitis, bilirubin crys- strate concentric circles and radial striations (Fig. 7-96). They tals may be found incorporated into the matrix of casts. are seen less frequently than tyrosine crystals and, when pres- ent, should be accompanied by tyrosine crystals. Sulfonamide Crystals Bilirubin crystals are present in patients with hepatic disor- Before the development of more soluble sulfonamides, the ders, producing large amounts of bilirubin in the urine. They finding of these crystals in the urine of patients being treated appear as clumped needles or granules with the characteristic for UTIs was common. Inadequate patient hydration was and  Chapter 7 | Microscopic Examination of Urine 209 include needles, rhombics, whetstones, sheaves of wheat, and rosettes with colors ranging from colorless to yellow-brown (Figs. 7-98 and 7-99). A check of the patient’s medication his- tory aids in the identification confirmation. Ampicillin Crystals Precipitation of antibiotics is not encountered frequently except for the rare observation of ampicillin crystals after massive doses of this penicillin compound without adequate hydration. Ampicillin crystals appear as colorless needles that tend to form bundles after refrigeration (Fig. 7-100 A and B). Knowledge of the patient’s history can aid in the identification. Urinary Sediment Artifacts Figure 7–96 Leucine crystals (×400). Notice the concentric Contaminants of all types can be found in urine, particularly circles. in specimens collected under improper conditions or in dirty containers. The artifacts encountered most frequently include starch, oil droplets, air bubbles, pollen grains, fibers, and fecal contamination. Because artifacts frequently resemble pathological elements, such as RBCs and casts, artifacts can present a major problem to students. Often, they are very highly refractile or occur in a different microscopic plane than the true sediment constituents. The reporting of artifacts is not necessary. A Figure 7–98 Sulfa crystals in rosette form (×400). B Figure 7–97 A and B. Bilirubin crystals. Notice the classic bright yellow color (×400). still is the primary cause of sulfonamide crystallization. The appearance of sulfonamide crystals in fresh urine can suggest the possibility of tubular damage if crystals are forming in the nephron. Currently a variety of sulfonamide medications is on the market; therefore, one can expect to encounter a variety of Figure 7–99 Sulfa crystals, WBCs, and bacteria seen in UTI crystal shapes and colors. Shapes encountered most frequently (×400). 210 Part Two | Urinalysis Oil droplets and air bubbles also are highly refractile and may resemble RBCs to inexperienced laboratory personnel. Oil droplets may result from contamination by immersion oil or lotions and creams and may be seen with fecal contamination (Fig. 7-102). Air bubbles occur when the specimen is placed under a cover slip. The presence of these artifacts should be considered in the context of the other urinalysis results. Pollen grains are seasonal contaminants that appear as spheres with a cell wall and occasional concentric circles (Fig. 7-103). Like many artifacts, their large size may cause them to be out of focus with true sediment constituents. Hair and fibers from clothing and diapers initially may be A mistaken for casts (Figs. 7-104, 7-106, and 7-107), though usually they are much longer and more refractile. Examination under polarized light frequently can differentiate between fibers and casts (Fig. 7-105). Fibers often polarize, whereas casts, other than fatty casts, do not polarize. Technical Tip 7-20. Use polarized microscopy to dif- ferentiate between fibers, which polarize, and casts, which do not (except for fatty casts). B Figure 7–100 Ampicillin crystals. A. Nonrefrigerated ampicillin crystals. (×400). B. Ampicillin crystals after refrigeration (×400). Contamination from starch granules may occur when cornstarch is the powder used in powdered gloves. The gran- ules are highly refractile spheres, usually with a dimpled cen- ter (Fig. 7-101). They resemble fat droplets when polarized, producing a Maltese cross formation. Also starch granules may occasionally be confused with RBCs. Differentiation between starch and pathological elements can be made by considering other urinalysis results, including chemical tests for blood or protein and the presence of oval fat bodies or fatty casts. Figure 7–102 Fecal material and oil artifacts (×400). Figure 7–101 Starch granules. Notice the dimpled center (×400). Figure 7–103 Pollen grain. Notice the concentric circles (×400).  Chapter 7 | Microscopic Examination of Urine 211 Figure 7–107 Vegetable fiber on top of a hyaline cast. Figure 7–104 Fiber and squamous epithelial cell (×400). Figure 7–105 Fiber under polarized light (×100). Figure 7–108 Vegetable fiber resembling waxy cast (×400). For additional resources please visit www.fadavis.com References 1. Mynahan, C: Evaluation of macroscopic urinalysis as a screening procedure. Lab Med 15(3):176–179, 1984. 2. Tetrault, GA: Automated reagent strip urinalysis: Utility in re- ducing work load of urine microscopy and culture. Lab Med 25:162–167, 1994. 3. Clinical and Laboratory Standards Institute: Urinalysis; Approved Guideline, ed 3. CLSI document GP16-A3. Clinical and Labora- tory Standards Institute, Wayne, PA, 2009, CLSI. Figure 7–106 Diaper fiber resembling a cast. Notice the refractility 4. Schumann, GB, and Tebbs, RD: Comparison of slides used for (×400). standardized routine microscopic urinalysis. J Med Technol 3(1):54–58, 1986. Specimens that are collected improperly or, rarely, the 5. Addis, T: The number of formed elements in the urinary presence of a fistula between the intestinal and urinary tracts sediment of normal individuals. J Clin Invest 2(5):409–415, 1926. may produce fecal specimen contamination. Fecal artifacts may 6. Sternheimer, R, and Malbin, R: Clinical recognition of pyelonephri- appear as plant and meat fibers or as brown amorphous mate- tis with a new stain for urinary sediments. Am J Med 11:312–313, rial in a variety of sizes and shapes (Fig. 7-108). 1951.