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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.
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Cells of hematologic origin in
urine sediment
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Cells of epithelial origin in urine
sediment
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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.
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.
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
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laboratorymedicine> march 2001> number 3> volume 32
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B
A
B
B
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.
Glitter Cells
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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 µm 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.
Eosinophils
Although difficult to recognize in the
usual wet preparation of the urine sedi-
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.
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
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-
laboratorymedicine> march 2001> number 3> volume 32
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 µm), 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.
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[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
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.
Clue Cells
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.
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-
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laboratorymedicine> march 2001> number 3> volume 32
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.
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.
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.
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