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Chemistry, toxicology & urinalysis

Urine & renal function

Urine crystals & microscopy

Author: Archana Shetty, M.B.B.S., M.D.

Editorial Board Member: Melissa R. George, D.O.

Deputy Editor-in-Chief: Patricia Tsang, M.D., M.B.A.

Last author update: 2 August 2022

Last staff update: 2 August 2022

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Table of Contents

Cite this page: Shetty A. Urine crystals & microscopy. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/chemistryurinecrystals.html. Accessed May 30th, 2023.

Definition / general

Standard component of complete urinalysis
One of the oldest laboratory tests in medicine is to look for abnormal microscopic constituents in urine (JAMA Netw Open 2020;3:e2013959)

Essential features

Urine analysis is the third major diagnostic screening test in the clinical laboratory, only preceded by serum / plasma chemistry profiles and complete blood count analysis
As sample collection is done by the patient, it is more likely to be susceptible to preanalytical issues
Routine urine microscopic examination includes looking for cellular, formed elements and organisms

Diagrams / tables

Contributed by Archana Shetty, M.B.B.S., M.D.

Urine sediment microscopy

Steps in urine dipstick test

Indications for testing

Helps diagnose:
- Kidney disease
- Urinary tract infection
- Cancers of urinary tract
- Reactions to medicines
- Prostate infection
- Liver disease
- Yeast, viral, parasitic infections

Laboratory

Specimen for testing:
- First void urine preferred in routine practice
- Midstream urine is the most appropriate sample, since contaminating elements, such as bacteria, analytes and formed particles, are minimized
Collection instructions:
- Clean catch urine or midstream portions of first morning urine
- Samples should be collected in a wide mouthed, sterile container made of nonabsorbing materials, with no influence on any analyte
- Due to influence on the viability of bacteria, the use of soap or antiseptics while washing the genitalia is not recommended (Ann Biol Clin (Paris) 2018;76:609)
- Catheter urine sample for bacteriological study or culture in bed ridden patients or patients with obstruction of urinary tract
- For infants, a clean plastic bag can be attached around genitalia and left in place for some time for sample to be collected
Volume required:
- 12 mL is the recommended urine volume for adult patients
- Range of 5 - 12 mL of urine is acceptable to examine the formed elements in urine
- Test protocol and acceptance of smaller urine specimens is determined by the individual laboratory
Procedure:
- Centrifuge urine at 1,500 rpm for 10 minutes
- Resuspend sediment in 1 drop of urine an observe under microscope
- Examine first using low power and then high power
- Lower the condenser and minimize the light to view elements
Possible interferences:
- Dietary intake, exercise
- Medications
- Increased time lag between sampling and analysis
  - For urinalysis that cannot be performed within 2 hours of collection
    - Lack of temperature control and lack of addition of a preservative to samples will lower the quality of urinary test results
    - If testing by strip method, test can be performed within 24 hours if urine is refrigerated without preservatives (Biochem Med (Zagreb) 2014;24:89)

Types of elements in urine

Urinary crystals:
- Crystals are formed in urine when it is supersaturated with certain minerals, which may be due to
  - Increased excretion of these constituents
  - Reduced urine volume, an alteration in urine pH
  - A combination of the above factors
- Crystals can be seen in both healthy and disease states

Normal crystals
Crystals	Ph of urine	Identification	Remarks
Uric acid	Acidic	Barrels, rosettes, rhomboids, needles or hexagonal plates Amber in color Soluble in alkali	Urate nephrolithiasis or acute urate nephropathy, gout and leukemia
Calcium oxalate	Acidic or alkaline	Can be bihydrate (envelope shape) or monohydrate (ovoids, dumbells or rods)	Dietary oxalate ingestion (spinach, tomato, cabbage and asparagus) and nephrolithiasis
Calcium phosphate	Alkaline	Large, flat shaped plates or wedge shaped prisms Prisms often appear in rosettes	In rare cases, could be caused by hypoparathyroidism
Triple phosphate	Alkaline	Coffin lid appearance Made of magnesium ammonium and phosphate	In patients with struvite stones and in urinary tract infection with Proteus
Calcium carbonate	Alkaline	Spheroids with radial striations Colorless to yellow-brown Readily observed at low magnification	Normal
Ammonium biurate	Alkaline	Thorn apple appearance Yellow-brown with irregular protrusions or spiky thorns	Old or longstanding urine sample
Amorphous	Phosphates - seen in alkaline urine and soluble in acetic acid	Fine granular material with no definite shape Differentiated based on pH	Can be confused with degenerating cells

Abnormal crystals
Crystals	Ph of urine	Identification	Remarks
Bilirubin	Acidic	Needle-like or granular crystals Dark brown in color	Associated with increased conjugated bilirubin, severe liver disorders of obstructive cause
Cholesterol	Acidic	Colorless and refractile with notched corners Step ladder pattern Soluble in alcohol	Nephrotic syndrome
Cysteine	Acidic	Monomorphic, colorless, hexagonal plates that resemble benzene rings Soluble in alkali, especially ammonia	Genetic disease - cysteinuria (Nephrol Ther 2015;11:174)
Leucine	Acidic / neutral	Concentric circles with radial striations Yellow-brown in color Resembles a cross section of a tree trunk Soluble in alkali	Liver disorders with impaired amino acid metabolism
Tyrosine	Acidic / neutral	Colorless, yellow fine needles	Liver disorders with impaired amino acid metabolism
Sulfonamide	Acidic / neutral	Sheaves of small needles or spheroids Soluble in acetone	Drug related

Urinary casts:
- Casts are cylindrical, cigar shaped microscopic structures composed mainly of mucoprotein (Tamm-Horsfall mucoprotein, also known as uromodulin) that is secreted by epithelial cells lining the loops of Henle, the distal tubules and the collecting ducts
- As they are formed in the distal and collecting tubules, their presence in urine suggests renal parenchymal pathology
- Named depending on the predominant constituent
- Reported as number seen per low power field (10x objective)

Noncellular casts
Type of cast	Appearance	Remarks
Hyaline	Appear colorless Cylindrical with parallel sides Made of Tamm-Horsfall mucoprotein with smooth texture and a refractive index very close to that of the surrounding fluid	Seen normally (not associated with disease states); seen after strenuous exercise and with nonrenal diseases, such as dehydration (EJIFCC 2021;32:410)
Granular	Composed of degenerated cellular debris, mainly of renal tubular epithelial cells embedded in Tamm-Horsfall protein	Seen in acute glomerulonephritis and pyelonephritis; appears muddy brown in acute tubular necrosis
Waxy	Formed due to prolonged stasis of hyaline casts Homogenous glassy appearance, with serrated margins Ends are straight and sharp, unlike other casts	Final stage of cast degeneration: indicates tubular injury of a more chronic nature than granular or cellular casts and is likely associated with low urine flow; always of pathologic significance (associated with end stage renal failure)
Fatty	Cylindrical structures mainly comprised of fat globules and lipid droplets within a protein matrix	Seen in nephrotic syndrome; may represent tubular degeneration

Cellular casts
Type of cast	Appearance	Remarks
White blood cell (WBC)	Cylindrical structures mainly comprised of WBCs embedded in protein matrix	Comprised of neutrophils and seen in tubulointerstitial diseases, such as acute pyelonephritis; indicates focus of infection as kidney
Epithelial	Composed of renal epithelial cells	Seen in acute tubular necrosis, viral diseases (such as infection with cytomegalovirus) and exposure to nephrotoxic substances (such as mercury, ethylene glycol and various drugs [with the same conditions as when associated with renal epithelial cells]); closely resembles granular casts
Red blood cell (RBC) / hemoglobin	Formed when RBCs are trapped in mucoprotein matrix Degeneration of blood cells within cast matrix forms hemoglobin cast (red-brown color)	Presence of even a single cast is significant and indicates intrarenal hemorrhage, glomerulonephritis, acute tubular necrosis or renal ischemia

Cells:
- Reported as the number of each type found per average high power field (HPF)

Cell type	Description	Remarks
Renal tubular epithelial	Renal tubular cells from the renal pelvis, ureter or bladder (polyhedral, columnar or oval) Have granular cytoplasm with a single, large, refractile, eccentric nucleus	Tubular damage (like acute tubular necrosis) pyelonephritis, viral infection of kidney, allograft rejection and salicylate or heavy metal poisoning (Clin J Am Soc Nephrol 2010;5:402)
Transitional epithelial	Large and diamond or pear shaped (caudate cells)	Seen after catheterization and in transitional cell carcinoma
Squamous epithelial	Can be squamous cells lining from skin surface urethra Large cells that are rectangular in shape Flat with abundant cytoplasm Small, central nucleus	Large numbers - urine is contaminated with vaginal fluid
White blood	Have lobed nuclei and granular cytoplasm 10 - 15 μm in size Normal: 0 - 2/HPF Greater than 10/HPF or presence of clumps is suggestive of urinary tract infection	Infection in either the upper or lower urinary tract or with acute glomerulonephritis, tubule interstitial nephritis
Red blood	Disc shaped refractile structures about 7 μm in size Crenated in concentrated urine and swollen in hypotonic urine Theoretically no RBCs must be seen; if 1 or more red cells can be found in every HPF and if contamination can be ruled out, the specimen is probably abnormal Note: to differentiate - adding acetic acid to the sediment lyses the RBCs and leaves behind yeast, oil droplets and air bubbles	Seen in glomerular damage, tumors which erode the urinary tract anywhere along its length, kidney trauma, urinary tract stones, renal infarcts, acute tubular necrosis, upper and lower urinary tract infections, nephrotoxins and physical stress RBCs may contaminate the urine from the vagina in menstruating women or from trauma produced by bladder catheterization > 80% of dysmorphic RBCs indicate glomerular disease (e.g., acute glomerulonephritis)
Oval fat body	Desquamated tubular epithelial cells laden with fat	Seen in nephrotic syndrome

Organisms:

Organism	Description	Remarks
Bacteria	Escherichia coli and Klebsiella pneumoniae are the most common bacteria found Cocci or rods	In a wet preparation, presence of bacteria should be reported only when urine is fresh; presence of only bacteria without pus cells indicates contamination with vaginal or skin flora
Yeast cells	Round or oval structures of approximately the same size as red blood cells In contrast to red cells, yeast cells show budding, are oval, are more refractile and are not soluble in 2% acetic acid	Seen in immunocompromised state, vaginal candidiasis or diabetes mellitus
*Trichomonas vaginalis*	Motile organisms with pear shape, undulating membrane on 1 side and 4 flagella Easily detected in fresh urine due to their motility	Causes vaginitis in females and are thus contaminants in urine Note: wet preparation of genital secretions or wet mount is the diagnostic method of choice (Sci Rep 2019;9:11074)
*Schistosoma haematobium*	Ova are elongated and are 60 x 160 microns They are slightly transparent and have a delicate, terminal spine	Rarely seen in urine
Enterobius vermicularis (pinworm)	Ova are ovoid in shape and smooth with 1 side flattened	Not a urinary parasite; can be present in the urine sediment as a fecal contaminant

Miscellaneous:

Element	Description	Remarks
Sperm	Appears immotile in urine as it cannot survive	Significant in infertility cases and sexual abuse May be seen in males after a nocturnal emission or ejaculation Presence in the urine is of significance in the case of retrograde ejaculation

Automated urine analyzers

Automated urine analyzers enhance productivity and efficiency in the laboratories by increasing the reproducibility and throughput and reducing potential human errors
Reduces the time and labor required to process urine samples
Automated analyzers help standardize analysis so that laboratories can accurately recognize pathological elements in urine (Clin Chem Lab Med 2015;53:s1509)
One study comparing 3 automated urine analyzers (Roche's Cobas 6500, Sysmex's UN3000-111b and Iris's iRICELL 3000) showed fairly good correlation among the 3 platforms and with manual microscopy (Pract Lab Med 2021;24:e00203)
However, microscopic confirmation by experienced technologists is still necessary to avoid errors and definitively classify urine sediments, especially in pathologic specimen samples and images (particularly dysmorphic cells, bacteria, yeasts, casts and crystals)

Urine reagent strips

Urine strips are firm, plastic strips onto which several separate reagent areas are affixed
Analytes detected can be ascorbic acid, glucose, bilirubin, ketone (acetoacetic acid), specific gravity, blood, pH, protein, urobilinogen, nitrite and leukocytes
Reagent strips are packaged along with a drying agent in a plastic bottle with a twist off cap
Each strip is stable and ready to use upon removal from the bottle
Entire reagent strip is disposable
Results are obtained by direct comparison of the test strip with the color blocks printed on the bottle label
Procedure:
- Completely immerse reagent areas of the strip in fresh, well mixed urine
- While removing, touch the side of the strip against the rim of the urine container to remove excess urine
- Blot the lengthwise edge of the strip on an absorbent paper towel to further remove excess urine and avoid running over
- Compare each reagent area to its corresponding color blocks on the color chart and read at the times specified
  - Proper read time is critical for optimal results
- Interpretation of microscopic findings can be correlated with strip findings for better interpretation

Microscopic (histologic) images

Contributed by Archana Shetty, M.B.B.S., M.D.

Calcium oxalate crystals

Uric acid crystals

Sulfa drug crystals

Triple phosphate crystals

Squamous epithelial cells

Red blood cells

Red blood cell casts

Amorphous urates in urine

Board review style question #1

A urine sample from a 38 year old man with alcohol induced cirrhosis, ascites and jaundice is shown above. The appearance of the crystal is golden brown, with specific gravity = 1.015 and pH = 6.0. Identify the sediment finding (arrow)

Cholesterol crystals
Cysteine crystals
Leucine crystals
Tyrosine crystals

Board review style answer #1

C. Leucine crystals are seen in acidic urine. They appear as concentric circles with radial striations and are yellow-brown in color. They resemble a cross section of a tree trunk and are associated with liver disorder.

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Reference: Urine crystals & microscopy

Board review style question #2

Which of the following types of urinary cast has serrated edges and is an indicator of end stage renal disease?

Fatty cast
Granular cast
Waxy cast
White blood cell (WBC) cast

Board review style answer #2

C. Waxy cast is seen in the setting of prolonged low urine flow.

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Reference: Urine crystals & microscopy

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