Urinalysis Review A Complete Urinalysis

and Case Studies

John H. Landis, MS, MLS(ASCP)
Adjunct Professor, University of Cincinnati
Adjunct Professor, Oakland University
p Three Parts
Professor Emeritus, Ferris State University
n Physical Examination
n Chemical Examination
n Microscopic Examination––Omitted in
some laboratories if the physical and
chemical exams are “normal”

Meglumine Waxy Cast Uric Acid

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Brunzel, N.A., Saunders, 2013

Drugs Causing Color Change in Urine

Brunzel, N.A., Saunders, 2013

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Common Causes of Cloudiness in Urine Chemical Examination by
Reagent Strips

p Principles of tests differ

depending on the reagent
strip brand:
n Multistix by Siemens
n Chemstrip by Roche
p Many similarities; a few
important differences
p Reagent strip readers
Brunzel, N.A., Saunders, 2013 standardize color
interpretation

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Brunzel, N.A., Saunders, 2013

Correlations Between Exams Correlation between

– serve as limited QC checks Chemical and Microscopic Exams
p Physical and Chemical Exams
n Color with SG, blood, or bilirubin
Example: red color expect positive blood

p Physical and Microscopic Exams

n Clarity with amount of microscopic entities
Example: cloudy urine expect significant number of microscopic
entities

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Brunzel, N.A., Saunders, 2013 Brunzel, N.A., Saunders, 2013

Age: 40 Sex: M Clinical Info: ED, severe back and

Chemical Examination: Case##1
Case abdominal pain; CBC and Amylase normal

Reagent Strip Tests

Color Yellow Glucose Neg Clinitest

p Specific Gravity (SG) p Glucose
p pH p Ketone Appearance Hazy Protein Trace SSA:

p Blood (heme) p Bilirubin

Specific 1.030 Ketones Neg
p Protein (albumin) p Urobilinogen Gravity
p Leukocyte Esterase pH 5.0 Bilirubin Neg Ictotest:
p Nitrite
Blood 2+
2+ Urobilinogen Normal
• screening tests • indicate metabolic disorder
Nitrite Neg Leuk Est Neg

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Microscopic : 0-5 WBCs/hpf ; 10-25 ???? /hpf; unidentified crystals present 12

Brunzel, N.A., Saunders, 2013

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Case # 1 Case # 1

Calcium Oxalate – monohydrate Calcium oxalate - dihydrate

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Red compensated Polarized light

Case # 1

p What abnormal findings are present:

n 2+ Blood and 10-25 RBCs/hpf

p What are causes of the findings:

n Bleeding in the genitourinary tract
p Trauma, inflammation, calculi, tumors

p Why are the RBCs so weird looking?

n Crenated due to the high Sp. Gr.

Calcium oxalate monohydrate

p Why CBC and Amylase?
17 n Doc is checking for appendicitis and pancreatitis 18

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 Chemical Exam: Blood (heme)

Hgb
H2O2 + Chromogen* Oxidized + H2O
Mgb chromogen

*tetramethylbenzidine

Hgb = Hemoglobin
Mgb = Myoglobin
Renal Calculi 19 20

Chemical Exam: Blood (heme) NOTE

p Principle: pseudoperoxidase activity of the heme moiety If microscopic examination is NOT

p Equally detects: hemoglobin, myoglobin performed, microscopic hematuria can be
p Chemstrip results are not affected by ascorbic acid missed when ascorbic acid is present
interference due to an iodate scavenger pad that
overlays test pad
p Other brands can give a false negative or lower result if
Why? Ascorbic acid reduces the H2O2 on the
ascorbic acid is present (≥ 9 mg/dL)
reaction pad, preventing oxidation of the
chromogen by any heme present

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Undetected If RBCs present, but reagent

Microscopic Hematuria strip Blood test is negative

p Retrospective study* of 709 consecutive urine p Check for ascorbic acid (Chemstrip not affected);
specimens report accordingly
p Microscopic hematuria was present in 204 p Retest specimen for blood using well-mixed,
specimens (29%) unspun urine
p Chemical test for blood was negative in 21% p Ensure no sample mix-up has occurred
(43/204) of these samples between phys/chem and micro exam
p If only the reagent strip blood test is used, p Re-evaluate identity:
microscopic hematuria can be missed. n Are the RBCs really crystals? Check using
polarizing microscopy.
n Are the RBCs really yeast? Stain.
*Brunzel NA, Berry DE. Omitting the microscopic examination of urine: what is missed?
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Abstract MP10.45, IFCC-FESCC European Congress, May 2005

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 Age: 56 Sex: F Clinical Info: Urology clinic for
Case##2
Case intravenous pyelogram

Color Yellow Glucose Neg Clinitest

Appearance Hazy Protein Trace SSA: 4+

Specific >1.035
>1.035 Ketones Neg
Gravity
pH 6.0 Bilirubin Neg Ictotest:

Blood Neg Urobilinogen Normal

Nitrite Neg Leuk Est Neg

Microscopic : 0-5 WBCs/hpf ; Unidentified crystals present 25 26

Case # 2

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Case # 2

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Case # 2 Case # 2

p What are the abnormal findings:

p Discrepancies
n Specific Gravity n Trace protein, but 4+ SSA
n 4+ SSA
n Unidentified Crystals
p Causes of Discrepancies
n Radiographic dye is not detectable by strip

p Possible causes of abnormals: p Accurate Specific Gravity

n New specimen or Use Strip Sp. Gr.
n Tech Error on Sp. Gr.
n Crystals - Drugs
p Crystals ???
n Radiographic contrast dye crystals
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Age: 13 Sex: M Clinical Info: Severe back and

Case##3
Case abdominal pain; both father and uncle are Case # 3
kidney stone formers

Color Yellow Glucose Neg Clinitest

Appearance Hazy Protein Trace SSA:

Specific 1.015 Ketones Neg

Gravity
pH 6.0 Bilirubin Neg Ictotest:

Blood 2+
2+ Urobilinogen Normal

Nitrite Neg Leuk Est Neg

Microscopic : 0-5 WBCs/hpf ; 25-100 ????? /hpf; Unidentified crystals present 33 34

Case # 3 Case # 3

p Abnormal findings:
n Blood - pad and RBCs
n Cystine crystals

p Cause of Abnormals:
n Damage (kidney to urethra)
Polarizing filter trauma, infection, tumor, calculi
p Physiologic Abnormality
n Cystinuria
Defective reabsorption of Amino Acids
Inherited ; usually shows age 20-30s
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 Age: 14 Sex: M Clinical Info: 3 wks prior sore throat with
Case # 3 Case##4
Case Positive culture for b hemolytic strep. Now weakness,
Anorexia, headache and puffy eyelids. Oliguria present

p Additional AA found in the urine in cystinuria

Color Red
Red- Glucose Neg Clinitest
n Leucine, ornithine and arginine
Brown
Appearance Cloudy
Cloudy Protein 300mg/dL SSA:
300 3+
3+
mg/dL
p Cystinosis
Specific 1.025 Ketones Neg
n Inherited metabolic disorder with intracellular Gravity
deposition of cystine in all cells pH 6.0 Bilirubin Neg Ictotest:
n Particular damage to the kidney, eye, marrow and
spleen Blood 3+ Urobilinogen Normal
n Evident within first year of life Nitrite Neg Leuk Est Neg

37 Microscopic : 0-5 WBCs/hpf ; 10-25 ????? /hpf; 0-5 ????? /lpf (2 types) 38

Case # 4 Case # 4

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Case # 1 Case # 4

p Abnormal findings & Discrepancies

n Red-Brown, Cloudy, Large Blood

Protein, RBCs, RBC casts, Hemoglobin casts

p Morphology of RBCs
n Dysmorphic RBCs

p Likely Diagnosis?
Dysmorphic RBCs – Glomerular or tubular bleeding n Post-streptococcal Acute Glomerulonephritis
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 Age: 7 Sex: F Clinical Info: History of recent infections.
Case##5
Case Facial and general edema; urine pale and there is white foam Case # 5

Color Straw Glucose Neg Clinitest

Appearance Hazy Protein >2000

> 2000 SSA: 4+
mg/dL
Specific 1.020 Ketones Neg
Gravity
pH 6.0 Bilirubin Neg Ictotest:

Oil Red O Stain

Blood Neg Urobilinogen Normal

Nitrite Neg Leuk Est Neg

Microscopic : 0-5 WBCs/hpf ; 0-5 ????? /hpf; 0-5 ????? /lpf (2 types) 43 44

Case # 5 Case # 5

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Case # 5
Protein Reagent Strip Test
p Abnormal findings:
n Oval fat bodies
Protein error of indicators
n Protein
n Fatty casts
n Hyaline casts Indicator + Protein pH 3 H+ released
dye from indicator
p White foam?
n Albumin (blue-green)
p Edema?
n Hypoproteinemia

p Diagnosis?
n Nephrotic Syndrome
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 Protein Reagent Strip Test Microscopic Evidence of Fat

p Essentially specific for albumin; more sensitive to p Free floating fat globules
it than any other protein (e.g., hemoglobin,
myoglobin, mucoproteins, immunoglobulin light p Fat in cells (RTEs, WBCs, macrophages),
chains) called ‘oval fat bodies’ (OFB)
p Note that the amount of blood/hemoglobin in p Fat in casts, called ‘fatty casts’
urine must be greater than 5 -10 mg/dL (>
Large) before the protein test detects it
[Blood pad detection limit: 0.02 mg/dL]

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Fat should be confirmed before reporting

p Polarizing microscopy
n cholesterol forms characteristic maltese cross pattern
n triglyceride/neutral fat does NOT polarize

p Fat stains (Sudan III, Oil Red O)

n triglyceride/neutral fat stains characteristic orange (or
terra-cotta) color
n cholesterol does NOT stain

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Brunzel, N.A., Saunders, 2013

Always Correlate Exams

Urinary Fat (Lipiduria) – serves as a limited QC check
Chemical and Microscopic Exams
p Fat is always clinically significant
p If fat present, then albumin (protein)
must be present.
p Check for fat when protein is ~300 mg/dL
p If no albumin (protein) (and/or other
or greater using either
pathology), suspect specimen is
polarizing microscopy
n
contaminated with lotions, salves, etc.
n fat stains

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Age: 65 Sex: M Clinical Info: Diabetes (Type 1)

Case##6
Case with oliguria

In Summary
p Any condition/disease that alters the Color Yellow Glucose Neg Clinitest
selectivity (pore size) of the GFB
(glomerular filtration barrier) can result in Appearance Hazy Protein 300
300 SSA:
mg/dL
mg/dL
proteinuria and, if severe enough,
Specific 1.010 Ketones Neg
lipiduria Gravity

n Renal disease pH 6.0 Bilirubin Neg Ictotest:

n Metabolic disease
Blood Neg Urobilinogen Normal
n Conditions that cause blood pressure changes
Nitrite Neg Leuk Est Neg

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Microscopic : 0-5 WBCs/hpf ; 5-10 ????? /lpf; 60
Brunzel, N.A., Saunders, 2013

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Case # 6 Case # 6

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Age: 48 Sex: F Clinical Info: Emergency appendectomy

Case # 6 Case##7
Case with bleeding; transfused with 1 unit packed cells; 2 hrs later
developed fever, chills, 2 days later UA and Rous test

p Abnormal results Color Brown Glucose Neg Clinitest

n Protein
Appearance Sl Cloudy Protein 300 SSA:
n Broad and Waxy Casts mg/dL
p Confirmatory Microscopy Specific 1.015 Ketones Neg
Gravity
n Waxy casts will not light up with Polarized light
pH 5.0 Bilirubin Neg Ictotest:
p Cause of abnormal results
n Chronic Renal Failure Blood 3+ Urobilinogen 4 E.U./L Rous
p Why Broad and Waxy Casts? Test:
n Dilation of tubules and formation in the collecting ducts Nitrite Neg Leuk Est Neg Positive
Positive

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Microscopic : 0-5 WBCs/hpf ; 0-5 RBCs/hpf; 2-5 ???? /hpf 64

Case # 7 Case # 7
Unstained Iron Stain

Unstained Iron Stain

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Case # 7 Case # 7

p Abnormal findings & Discrepancies: p Brown color of urine ?

n Brown, Sl cloudy, 3+ blood, protein,
n Methemoglobin or urobilin
n Urobilinogen, Rous test , Unidentified objects

p Discrepancy: p Why urobilinogen?

n Blood on pad but no RBCs n Increased available in small intestine for
p Cause of discrepancy reabsorption because of hemolytic event
n Intravascular hemolysis – Hemoglobinuria or myoglobin
p No urine Bilirubin ?
p Hemosiderin? n Only conjugated bilirubin in urine
n Storage form of iron; iron entered renal tubular cells and
renal cells died
n Unconjugated bound to albumin and not filtered by
glomeruli
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Age: 32 Sex: M Clinical Info: Sinus infection treated with

Case##8
Case methicilin; patient developed severe edema Case # 8
Physician ordered a Hansel Stain on the sediment

Color Yellow Glucose Neg Clinitest

Appearance Cloudy Protein 300

300 SSA:
mg/dL
mg/dL
Hansel Stain
Specific 1.015 Ketones Neg
Gravity
pH 6.0 Bilirubin Neg Ictotest:

Blood 2+
2+ Urobilinogen Normal

Nitrite Neg Leuk Est Pos

Microscopic : 10-25 RBCs/hpf ; >100 ????/hpf; 0-5 ???? /lpf 69 70

Case # 8 Case # 8

p Abnormal findings & Discrepancies

n Cloudy, Blood, Protein, Leuk Esterase, WBCs,
Eosinophils, WBC casts

p Technique for Hansel stain

n Centrifuge or cytocentrifuge the urine stain
sediment with Wright’s or Hansel’s stain

p Cause of Abnormal results?

n Inflammatory reaction - interstitial nephritis

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 Age: 65 Sex: M Clinical Info: Construction worker
Case##9
Case admitted because of a fall and overnight his urine output Case # 9
drops while on IV fluids.

Color Brown Glucose Neg Clinitest

Appearance Hazy Protein 300

300 SSA: 1+
mg/dL
mg/dL
Specific 1.022 Ketones Neg
Gravity
pH 6.0 Bilirubin Neg Ictotest:

Blood 3+
3+ Urobilinogen Normal

Nitrite Neg Leuk Est Neg

Microscopic : 0-5 RBCs/hpf ; 0-5 ????/hpf; 10-25 ???? /lpf 73 74

Epithelial Cells
Epithelial Cells

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Case # 9
Renal epithelial cells
p Abnormal findings:
n Color, Appearance, blood, protein, Renal tubular epithelial
cells, hyaline casts

p Discrepancies:
n Blood on pad but no RBCs

p Cause of discrepancies?
n Hemoglobinuria or myoglobinuria

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 Age: 8 months Sex: M Clinical Info: Failure to thrive;
Case # 9 Case##10
Case Slow motor development; appearance of orange sand in
diapers

p Further testing ? Color Yellow Glucose Neg Clinitest

n Screen for Hgb vs Myoglobin
n CK and LD; visual of plasma Appearance Hazy Protein Neg SSA:

Specific 1.022 Ketones Neg

p Probable diagnosis? Gravity
pH 5.0 Bilirubin Neg Ictotest:
n Rhabdomyolysis with acute renal failure
Blood Neg Urobilinogen Normal

Nitrite Neg Leuk Est Neg

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Microscopic : 0-5 WBCs/hpf ; ???? crystals 80

Case # 10 Case # 10

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Case # 10 Case # 10

p Abnormal findings?
n Uric Acid crystals

p pH consistent?
n Yes, Uric acid seen in acid urine

p Diagnosis?
n Lesch-Nyhan disease
n sex-linked recessive
n Uric acid accumulation
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 Why dont I ever
Facts about Urine Crystals see these crystals?

p When solutes exceed their solubility, they Bilirubin crystals

can precipitate in various forms –– Cholesterol crystals
crystalline or amorphous Leucine crystals
p Factors contributing to crystal formation:
Tyrosine crystals
n Solute concentration
n pH Today, rapid turn-around-times as well
n Temperature as reduced refrigeration of specimens
n Urine flow prevents their precipitation.

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What is the pH? ACID (≤ 7.0)

p pH ≤ 5.7: think uric acid
n yellow to brown
n variety of shapes & sizes

p pH > 5.7: think urates

n amorphous urates––granular material

n monosodium urates––thin, colorless needles

n urate salts (K+, NH4+)––brown spheres &
clusters
n add glacial acetic acid––will convert to
uric acid
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 What is the pH? ALKALINE (> 7.0)

p Think phosphates
n Amorphous PO4-2––fine, granular material
n Triple phosphates––colorless, 3 to 6 sided
prisms
n Calcium phosphates
p colorless, thin prisms with one tapered
end; forms rosettes or stellar patterns
p colorless, thin sheets with irregular edges

n Ammonium biurate––yellow-brown spheres

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Triple phosphate 93 Triple phosphate 94

Calcium Phosphates 95 96
Ammonium biurate

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Many crystals present? Physiologically Possible pH
p pH 4.5 - 8.0
p Suspect medication or dietary p If pH < 4.5 or pH > 8.0, indicates:
supplement/excess with inadequate n iatrogenically induced (e.g., medication, IV
hydration imaging media)
n Check medications and recent procedures pH > 8.0; ammonium biurate crystals can be present
in “fresh, normal” urine
(e.g., radiographic, imaging)
n Evaluate patient history n improper storage/handling

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References
p Brunzel, N.A., Fundamentals of Urine and Body Fluid
Analysis, Saunders, 2013.

p Haber, et.al., Color Atlas of Urinary Sediment, CAP Press,

2010.

p Strasinger, S, Urinalysis and Body Fluids, F.A. Davis, 2007

p Simerville, J., et. al., Urinalysis: A Comprehensive Review,

American Family Physician, March 15, 2005,
www.aafp.org/afp

p landisj@gmail.com
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