Cells in Urine

3
laboratorymedicine> march 2001> numbe r 3> volume 32 153 © your lab focus This article describes the various cells that may be encountered in the urine sedi- ment. Each cell type is described in terms of the source or mechanism of formation, together with the pathologic or main clini- cal significance. Reagent-strip findings or other sediment findings associated with each cell type are also included. For mor- phologic 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 morpho- logic forms may be present [ I1]. The use of stains or phase-contrast microscopy is helpful in their identification. To deter- mine 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 pres- ence 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 indica- tion of glomerular involvement, as is seen with acute glomerular nephritis. 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 pres- ence 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 microsco py are helpful in their identifica tion. 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 pres- ent unless otherwise specified. Neutrophils in the urine sediment indicate inflammati on at some point along the uro- genital 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 indi- cated 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 nega- tive leukocyte esterase test result does not rule out disease. The reaction is specific for esterase, which is present in granulo- cytic 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 , nega- tive or lower levels of protein are more consistent with lower urinary tract infec- tions, while protein levels of 100 mg/dL or more indicate renal involvement. CE update [chemistry | hematology] Cells in the Urine Sediment  Karen M. Ringsrud, MT(ASCP) Fr om the Department of Laboratory Medicine and P athology ,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 qu estions and the corresponding answer form are loc ated af ter the “Your Lab Focus” s e ction, p 161. Cells of hematologic origin in urine sediment Cells of epithelial origin in urine sediment Microorganisms in urine sediment [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).

Transcript of Cells in Urine

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laboratorymedicine> march 2001> number 3> volume 32©

your lab focus

This article describes the various cells

that may be encountered in the urine sedi-

ment. Each cell type is described in terms

of the source or mechanism of formation,

together with the pathologic or main clini-

cal significance. Reagent-strip findings or

other sediment findings associated with

each cell type are also included. For mor-

phologic 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 morpho-

logic forms may be present [I1]. The use

of stains or phase-contrast microscopy is

helpful in their identification. To deter-

mine the cause and site of origin of the

RBCs, other information, both laboratoryand clinical, is needed. Information about

other sediment findings, such as the pres-

ence 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 indica-

tion of glomerular involvement, as is seen

with acute glomerular nephritis.

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 pres-

ence 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 pres-

ent unless otherwise specified.

Neutrophils in the urine sediment indicate

inflammation at some point along the uro-

genital 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 indi-

cated 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 nega-

tive leukocyte esterase test result does not

rule out disease. The reaction is specific

for esterase, which is present in granulo-cytic 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, nega-

tive or lower levels of protein are more

consistent with lower urinary tract infec-

tions, while protein levels of 100 mg/dL

or more indicate renal involvement.

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 af ter the “Your Lab Focus” section, p 161.

Cells of hematologic origin inurine sediment

Cells of epithelial origin in urinesediment

Microorganisms in urine sediment

[I1] Seven RBCs and 1 WBC (arrow). Note

granularity and variations of staining of thecrenated RBCs, making them difficult to

distinguish from WBCs (Sedi-Stain, ×400).

[I2] Seven WBCs and 1 RBC (arrow). Note thatthe 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).

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An even more reliable marker for

renal involvement is the presence of casts,

generally WBC or granular casts. If cer-

tain 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, pro-

statitis, or urethritis.

Glitter CellsGlitter 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 µm owing to

swelling. The cytoplasmic granules are in

constant motion (brownian), resulting in a

glittering appearance when a wet prepara-

tion is viewed microscopically. This is

especially apparent under phase-contrastillumination. These cells were formerly

thought to indicate chronic pyelonephri-

tis, but they are also seen in dilute urine

specimens from patients with lower uri-

nary tract infections.

 EosinophilsAlthough difficult to recognize in the

usual wet preparation of the urine sedi-

ment, eosinophils may be present. Detec-

tion is enhanced with the use of cytocen-

trifugation 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.

 LymphocytesAlthough they are rarely recognized, a

few small lymphocytes are normally pres-

ent 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, cytocentrifuga-

tion and staining with Wright or Papanico-

laou stain are indicated. The leukocyte

esterase test result is negative or unaffected

by the presence of lymphocytes.

Cells of Epithelial OriginRenal Epithelial Cells

A few renal epithelial cells, also

called renal tubular epithelium, may be

found in the urine of healthy persons be-

cause 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-

lial cells found in urine (renal, transitional

or urothelial, and squamous), renal ep-

ithelial cells are the most significant clini-

cally. 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 (espe-

cially aspirin), heavy metals, inflamma-

tion, 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 morpho-

logic characteristics vary depending on

the place of origin within the nephron.

They are especially difficult to distinguishfrom the small forms of transitional ep-

ithelial cells (urothelium). They are gen-

erally slightly larger to twice as large as a

neutrophil (20-35 µm), which is about the

same size as smaller transitional epithelial

cells, and have a distinct single round nu-

cleus [I4]. Inclusion bodies may be seen

in viral infections, such as rubella and her-

pes, and especially with cytomegalovirus.

Renal cells from the collecting tubules

tend to be polyhedral or cuboidal, as op-

posed to the rounded cells more typical of 

transitional epithelium. Renal cells de-rived from the proximal tubules are rela-

tively large, ovoid, or elongated granular

cells, which may be mistaken for small or

fragmented granular casts. Renal epithe-

lial 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 help-

ful distinction from neutrophils.

Oval Fat Bodies, Renal Tubular Fat,

or Renal Tubular Fat BodiesThese 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

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54

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your lab focus

[I3] Transitional epithelial cell (A), squamous epithelial cells (B), and eosinophils (C). Cytocentrifuged

preparation (rapid Wright stain, ×400 [enlarged]).

 A 

B

B

B

C

C

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with massive proteinuria as seen in

nephrotic syndrome. Aids to identifica-

tion include staining with fat stains such

as Sudan III or oil red O for triglyceridesor neutral fat, together with polarizing

microscopy for the presence of the typi-

cal Maltese cross appearance of choles-

terol 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 thebase 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 num-

bers 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, cyto-

logic examination with Papanicolaoustain 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 exter-

nal to the vagina. As a result, many of 

the squamous epithelial cells seen in

urine are the result of perineal or vaginal

contamination in females or foreskin

contamination in males. A few are com-

monly seen in most urine specimens,

and they are of little clinical importance

[I3]. The presence of large numbers of 

squamous cells in females generally in-

dicates vaginal contamination.

Clue CellsClue cells, another type of squamous

cell of vaginal origin, may be seen con-

taminating the urine sediment. This squa-

mous 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 MicroorganismsEncountered in the Sediment

Bacteria

Normally, urine is sterile, or free of 

bacteria. However, owing to contamina-

tion as the specimen is voided, most

urine contains a few bacteria. These bac-

teria multiply rapidly if the specimen is

left at room temperature. In properly col-

lected, midstream specimens, according

to Kunin,2 “the presence of many (prefer-

ably more than 20) obvious bacteria” per

hpf in a sediment concentrated 10 or 12

times represents a significant urinarytract 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 typ-

ically seen in urine of an alkaline pH.

Associated sediment findings include the

presence of WBCs (neutrophils) andcasts (WBC, cellular, granular, or bacter-

ial). Although infections are most often

due to gram-negative rods of enteric ori-

gin, infectious organisms may also be

gram-positive cocci.

 Yeast

Yeast may be seen in urine, espe-

cially as the result of vaginal contamina-

tion from female patients with yeast in-

fections. It is also associated with dia-

betes mellitus owing to the presence of 

urinary glucose. Yeast is a common con-

taminant, from skin and the environment,

and infections are a problem in debili-

tated and immunosuppressed or immuno-

compromised patients.

Conclusion

Major cells found in the urine sedi-

ment 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 morphologi-

cally. Reagent-strip tests for blood, pro-

tein, leukocyte esterase, and nitrite are

especially helpful in correct identifica-

tion 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.

[I4] Two renal epithelial cells (cuboidal type) andseveral degenerating RBCs and WBCs (Sedi-

Stain, ×400).

Suggested Reading

College of American Pathologists.

Surveys Hematology Glossary .

Northfield, IL: College of AmericanPathologists, 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.

Linné JJ, Ringsrud KM. Clinical 

Laboratory Science: The Basics and 

Routine Techniques. 4th ed. St Louis,

MO: Mosby, 1999.

Ringsrud KM, Linné JJ. Urinalysis and 

Body Fluids: A Color Text and Atlas. St

Louis, MO: Mosby, 1995.