Urine Sediment of the Month: RBC “Lookalikes”

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Red blood cells (RBCs) in the urine are normally 7-8 µm in diameter, circular or slightly oval and biconcave in appearance. They may appear crenated, with symmetric spiked membrane contour in hypertonic urine, or spherical, with near loss of pigmentation, in hypotonic urine. As RBCs traverse areas of damaged glomerular basement membrane, they may sustain damage which ultimately results in dysmorphic forms such as acanthocytes: ring form RBC’s with one or more cytoplasmic protrusions, or “blebs”.

Although RBCs are usually easy to identify, there are numerous RBC lookalikes which may at times be difficult to discern from RBCs. These include:

  • Calcium oxalate monohydrate crystals
  • Lipid droplets
  • Starch granules
  • Yeast
  • Air bubbles
  • Spermatozoa heads
  • Squamous epithelial cell nuclei
  • Pollen

Calcium Oxalate Monohydrate Crystals
Calcium oxalate monohydrate crystal morphology is quite variable and at times these crystals may appear as small biconcave discs resembling RBC’s. When they are present within casts they are important to differentiate from RBC casts. Under polarized light they typically show polychromatic birefringence, whereas RBCs are not birefringent at all. When polarization is not available, darkfield may be useful. Calcium oxalate monohydrate crystals (as well as most crystals) have a high refractive index resulting in a “bright” appearance under dark-field illumination. RBCs under darkfield illumination appear as just a faint outline of the cell membrane.

Cast with round inclusions (brightfield above and polarized below, with SM stain) which look like RBCs until viewed under polarized light, where they are strongly birefringent confirming they are calcium oxalate monohydrate crystals and not RBCs

Lipid Droplets

Lipid droplets also appear as round or spherical objects but they vary in size from one droplet to another which is the main clue to their identity. In addition,  under polarized light they manifest a distinct “Maltese cross” pattern of birefringence. Under darkfield illumination they appear “bright” due to their high refractive index, unlike RBCs. 

Lipid cast (bright field, left and polarized, right) – note that the lipid droplets within the cast vary considerably in size and are spherical. They display a symmetrical “Maltese Cross” pattern under polarized light.

Artifacts

Artifact from lotions and lubricants may appear similar to lipid droplets, spherical and with varying sizes, but they are either not birefringent under polarized light or show only a partial irregular “Maltese Cross.”

Hand lotion artifact – brightfield

 

Hand lotion artifact – polarized (note: irregular, partial maltese crosses)

Starch Granules

Starch granules are usually slightly larger than typical RBCs and often have a central cleft. They have an irregular “Maltese cross” pattern under polarized light.

Starch granules, under brightfield (top image), darkfield (middle image), and polarized light (bottom image). Note: the irregular shape and central cleft which are characteristic of starch granules. Under polarized light they display an irregular, asymmetric “Maltese Cross” pattern.

Yeast

Yeast may be difficult to differentiate from RBCs at times. Clues to yeast include a more ovoid shape as well as “budding”. Indeed “budding” yeast may mimic the appearance of acanthocytes. The opposite is true as well. In fact, urine autoanalyzers (flow- imagers and flow cytometers) may occasionally misidentify acanthocytes as budding yeast! Another clue to the presence of yeast is formation of pseudohyphae.

Note the difference between acanthocytes (ring form, “doughnut” shaped RBCs with one or more cytoplasmic protrusions, or “blebs”, extending from either the exterior or interior of the torus shape) and the budding yeast (more ovoid, and light colored than RBCs, with no “doughnut hole”)

Other Objects Which May Appear Similar to RBCs:

  • Air bubbles are round or spherical but are variable in size and have a dark distinct outline unlike RBCs.
  • Spermatozoa, when the tails are no longer attached, may appear similar to RBCs but are usually somewhat smaller than typical RBCs and more ovoid.
  • The nuclei of squamous epithelial cells are generally the same size and shape of an RBC 
  • White blood cells, as they undergo degeneration may appear similar to RBCs
  • Pollen grains may have a similar shape but are usually considerably larger than RBCs
Color atlas of the urinary sediment : an illustrated field guide based on proficiency testing 

Meryl H. Haber MD, David Blomerg MD, Katherine Galagan MD, Eric F. Glassy MD, Patrick C.J. Ward MB BCh – College Of American Pathologists, c2010.

 

In order to differentiate RBC lookalikes from red blood cells it may be necessary to use different illumination modalities (such as phase contrast, darkfield, and polarization) as demonstrated in the accompanying images.

Biconcave appearing discs – brightfield, unstained
“Bright” appearance under darkfield illumination suggest these are crystals and not RBC’s
Under phase contrast we see these objects are within a cast
Polychromatic birefringence under polarized light confirms these are calcium oxalate monohydrate crystals

The importance of microscopy to distinguish RBCs and RBC mimickers is important given the clinical implications that RBCs can have.

Post by: Jay Seltzer

Reviewed by: Margaret DeOliveira, Samira Farouk

 

 

 

1 comment

  1. I have seen a few of these in my work. Only with time, you learn to differentiate them.

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