your lab focus CE update [chemistry | hematology]

Cells in the Urine Sediment

Karen M. Ringsrud, MT(ASCP) From the Department of Laboratory Medicine and Pathology,University of Minnesota Medical School, Minneapolis, MN
After reading this article, the reader should be able to describe the primary cells found in the urine sediment in terms of their origin and clinical relevance. Chemistry exam 0101 questions and the corresponding answer form are located after the Your Lab Focus section, p 161.

Cells of hematologic origin in urine sediment Cells of epithelial origin in urine sediment Microorganisms in urine sediment

This article describes the various cells that may be encountered in the urine sediment. Each cell type is described in terms of the source or mechanism of formation, together with the pathologic or main clinical significance. Reagent-strip findings or other sediment findings associated with each cell type are also included. For morphologic descriptions, the reader is referred to standard atlases and textbooks. Cells of Hematologic Origin Erythrocytes (RBCs) A few (<5) RBCs per high-power field (hpf) may be present in the urine of healthy persons. RBCs may be present in the urine as a result of bleeding at any point in the urogenital system from the glomerulus to the ureter. Various morphologic forms may be present [I1]. The use of stains or phase-contrast microscopy is helpful in their identification. To determine the cause and site of origin of the RBCs, other information, both laboratory and clinical, is needed. Information about other sediment findings, such as the presence of casts, and the presence of blood and protein on the reagent strip, is helpful. The presence of dysmorphic (or distorted) RBCs, especially when accompanied by proteinuria and RBC casts, is an indication of glomerular involvement, as is seen with acute glomerular nephritis.

[I1] Seven RBCs and 1 WBC (arrow). Note granularity and variations of staining of the crenated RBCs, making them difficult to distinguish from WBCs (Sedi-Stain, 400).

[I2] Seven WBCs and 1 RBC (arrow). Note that the WBCs are degenerating and only 1 shows a bilobed nucleus, making them difficult to distinguish from RBCs. The presence of 1 RBC is a helpful size marker (Sedi-Stain 400).

Leukocytes (WBCs) Theoretically, any of the WBCs found in blood might be present in the urine sediment. Neutrophils are most common, but lymphocytes and eosinophils have clinical significance and should be identified, if possible. The presence of a few (up to 5) WBCs per hpf is considered normal. They may be difficult to distinguish from RBCs [I2]. Stains or phase-contrast microscopy are helpful in their identification. Neutrophils The term leukocyte or WBC usually refers to the presence of a neutrophil (polymorphonuclear neutrophil, or PMN). It is assumed that this is the cell type present unless otherwise specified. Neutrophils in the urine sediment indicate inflammation at some point along the urogenital tract, and increased numbers are

seen in many urinary tract disorders. The presence of neutrophils is often associated with bacterial infection; however, either neutrophils or bacteria may be present without the other. The presence of neutrophils is indicated by a positive reagent-strip test result for leukocyte esterase. However, a positive reaction requires 5 to 15 cells per hpf in concentrated sediment; therefore, a negative leukocyte esterase test result does not rule out disease. The reaction is specific for esterase, which is present in granulocytic leukocytes (primarily neutrophils) and is not found in lymphocytes. The presence and degree of proteinuria (seen as a positive reagent-strip test result for protein) is also helpful. Generally, negative or lower levels of protein are more consistent with lower urinary tract infections, while protein levels of 100 mg/dL or more indicate renal involvement.

153

laboratorymedicine> march 2001> number 3> volume 32

 your lab focus

lial cells found in urine (renal, transitional or urothelial, and squamous), renal epithelial cells are the most significant clinically. They are associated with acute tubular necrosis, viral infections (such as cytomegalovirus), and renal transplant rejection. Their presence is also increased with fever, chemical toxins, drugs (especially aspirin), heavy metals, inflammation, infection, and neoplasms. Renal epithelial cells are the single layer of cells lining the nephron. These include cells lining the glomerulus, the proximal and distal convoluted tubules, and the collecting ducts. Recognition of renal epithelial cells is difficult, especially in the wet urine sediment, and morphologic characteristics vary depending on the place of origin within the nephron. They are especially difficult to distinguish from the small forms of transitional epithelial cells (urothelium). They are generally slightly larger to twice as large as a neutrophil (20-35 m), which is about the same size as smaller transitional epithelial cells, and have a distinct single round nucleus [I4]. Inclusion bodies may be seen in viral infections, such as rubella and herpes, and especially with cytomegalovirus. Renal cells from the collecting tubules tend to be polyhedral or cuboidal, as opposed to the rounded cells more typical of transitional epithelium. Renal cells derived from the proximal tubules are relatively large, ovoid, or elongated granular cells, which may be mistaken for small or fragmented granular casts. Renal epithelial cells are associated with a positive reagent-strip test result for protein and the presence of casts. They do not react with leukocyte esterase, and the reagent strip is negative in their presence; this is a helpful distinction from neutrophils. Oval Fat Bodies, Renal Tubular Fat, or Renal Tubular Fat Bodies These bodies are renal epithelial cells (or macrophages) that have filled with fat or lipid droplets. The fat may be either neutral fat (triglyceride) or cholesterol; they have the same significance clinically. Oval fat bodies indicate serious disease and should not be overlooked. They are often seen with fatty casts and fat droplets in the urine sediment and are associated

C C

[I3] Transitional epithelial cell (A), squamous epithelial cells (B), and eosinophils (C). Cytocentrifuged preparation (rapid Wright stain, 400 [enlarged]).

An even more reliable marker for renal involvement is the presence of casts, generally WBC or granular casts. If certain bacteria are present, the reagent-strip test result for nitrite may be positive. The finding of neutrophils in the absence of bacteria is problematic. It may indicate an infection with an organism not routinely cultured, such as Chlamydia species or tuberculosis. Alternatively, the neutrophils may be the response to inflammation, such as with stone formation, tumor, prostatitis, or urethritis.

ment, eosinophils may be present. Detection is enhanced with the use of cytocentrifugation and staining with Hansel stain, a special eosinophil stain (Lide Labs M) or with Wright stain [I3]. Eosinophils are associated with drug-induced interstitial nephritis, which is effectively treated by discontinuation of the drug, usually a penicillin or penicillin analogue.

Lymphocytes
Although they are rarely recognized, a few small lymphocytes are normally present in urine. They are about the same size as, and difficult to distinguish from, RBCs. Their presence has been used as an early indicator of renal rejection after transplant. When they are suspected, cytocentrifugation and staining with Wright or Papanicolaou stain are indicated. The leukocyte esterase test result is negative or unaffected by the presence of lymphocytes. Cells of Epithelial Origin Renal Epithelial Cells A few renal epithelial cells, also called renal tubular epithelium, may be found in the urine of healthy persons because of normal exfoliation. However, the presence of more than 15 renal tubular epithelial cells per 10 hpfs (430) is strong evidence of active renal disease or tubular injury.1 Of the 3 types of epithe-

Glitter Cells
Glitter cells are a type of neutrophil seen in hypotonic urine of specific gravity 1.010 or less. The neutrophil is larger than the usual 10 to 14 m owing to swelling. The cytoplasmic granules are in constant motion (brownian), resulting in a glittering appearance when a wet preparation is viewed microscopically. This is especially apparent under phase-contrast illumination. These cells were formerly thought to indicate chronic pyelonephritis, but they are also seen in dilute urine specimens from patients with lower urinary tract infections.

154

Eosinophils
Although difficult to recognize in the usual wet preparation of the urine sedi-

laboratorymedicine> march 2001> number 3> volume 32

 your lab focus

urine are the result of perineal or vaginal contamination in females or foreskin contamination in males. A few are commonly seen in most urine specimens, and they are of little clinical importance [I3]. The presence of large numbers of squamous cells in females generally indicates vaginal contamination. tion from female patients with yeast infections. It is also associated with diabetes mellitus owing to the presence of urinary glucose. Yeast is a common contaminant, from skin and the environment, and infections are a problem in debilitated and immunosuppressed or immunocompromised patients. Conclusion Major cells found in the urine sediment may originate from the blood, they may be epithelial cells lining the urinary tract, or they may be microorganisms such as bacteria or yeast. The cells may be difficult to distinguish morphologically. Reagent-strip tests for blood, protein, leukocyte esterase, and nitrite are especially helpful in correct identification of cells.
1. Schumann GB. Urine Sediment Examination. Baltimore, MD: Williams & Wilkins; 1980:83. 2. Kunin CM. Urinary Tract Infections: Detection, Prevention and Management. 5th ed. Baltimore, MD: Williams & Wilkins; 1997:59.

Clue Cells
[I4] Two renal epithelial cells (cuboidal type) and several degenerating RBCs and WBCs (SediStain, 400).

with massive proteinuria as seen in nephrotic syndrome. Aids to identification include staining with fat stains such as Sudan III or oil red O for triglycerides or neutral fat, together with polarizing microscopy for the presence of the typical Maltese cross appearance of cholesterol esters. Oval fat bodies may also be seen in the urine of patients with diabetic nephropathy or lupus nephritis. Transitional Epithelial Cells (Urothelial Cells) Transitional epithelial cells are the multilayer of epithelial cells that line the urinary tract from the renal pelvis to the distal part of the male urethra and to the base of the bladder (trigone) in females. They may be difficult to distinguish from renal epithelial cells, but they are generally larger and more spherical [I3]. A few transitional cells are present in the urine of healthy persons. Increased numbers are associated with infection. Large clumps or sheets of these cells may be seen with transitional cell carcinoma. Most often, urothelial cells are seen after urethral or ureteral catheterization. In the absence of such instrumentation, cytologic examination with Papanicolaou stain is indicated. Squamous Epithelial Cells Squamous epithelial cells line the urethra in females and the distal portion of the male urethra. The vagina is also lined with these cells as is the skin external to the vagina. As a result, many of the squamous epithelial cells seen in

Clue cells, another type of squamous cell of vaginal origin, may be seen contaminating the urine sediment. This squamous epithelial cell is covered or encrusted with a bacterium, Gardnerella vaginalis, indicating a bacterial vaginitis. Identification is performed on wet mounts of vaginal swabs. Some Microorganisms Encountered in the Sediment Bacteria Normally, urine is sterile, or free of bacteria. However, owing to contamination as the specimen is voided, most urine contains a few bacteria. These bacteria multiply rapidly if the specimen is left at room temperature. In properly collected, midstream specimens, according to Kunin,2 the presence of many (preferably more than 20) obvious bacteria per hpf in a sediment concentrated 10 or 12 times represents a significant urinary tract infection. Reagent-strip findings that suggest infection include positive test results for protein, leukocyte esterase, and nitrite. However, significant infection may be present with negative test results for nitrite depending on the infecting organism and whether sufficient time has passed (generally 4 hours) for conversion of nitrate to nitrite in the bladder. Certain (not all) bacteria are typically seen in urine of an alkaline pH. Associated sediment findings include the presence of WBCs (neutrophils) and casts (WBC, cellular, granular, or bacterial). Although infections are most often due to gram-negative rods of enteric origin, infectious organisms may also be gram-positive cocci. Yeast Yeast may be seen in urine, especially as the result of vaginal contamina-

Suggested Reading College of American Pathologists. Surveys Hematology Glossary. Northfield, IL: College of American Pathologists, 1999. Haber MH. Urinary Sediment: A Textbook Atlas. Chicago, IL: ASCP Press, 1981. Henry JB, Lauzon RL, Schumann GB. Basic Examination of Urine. In Henry JB, ed. Clinical Diagnosis and Management by Laboratory Methods. 19th ed. Philadelphia, PA: Saunders, 1996. Linn JJ, Ringsrud KM. Clinical Laboratory Science: The Basics and Routine Techniques. 4th ed. St Louis, MO: Mosby, 1999. Ringsrud KM, Linn JJ. Urinalysis and Body Fluids: A Color Text and Atlas. St Louis, MO: Mosby, 1995.

155

laboratorymedicine> march 2001> number 3> volume 32