rarwrDQRMICROSCOPIC EXAMINATION OF  20µL (0.

02 mL) covered by a 22 x 22 mm glass cover slip

 LPO
URINE o 10 fields
o Casts and composition of sediment
Factors affecting the Microscopic analysis:  HPO
 Methods by w/c sediment is prepared Commercial Systems
 V of sediment examined  Examples:
 Methods and equipment used to obtain o KOVA
visualization
o Urisystem
 Manner the results are reported
o Count-10
Macroscopic Screening: o Quick-Prep Urinalysis system
 Abnormalities on physical and chemical examination o CenSlide 2000 Urinalysis System
will lead to microscopic examination of the spx o Norwood
 Patient population should be considered when making  The packs given includes:
protocols for macroscopic screening: o Capped and calibrated centrifuge tubes
o Pregnant women o Decanting pipettes
o Pediatric and Diabetic px o Slide
o Immunocompromised  Cen-Slide
o Renal px o Provides a specially designed tube that
permits direct reading of urine sediment
MACROSCOPIC SCREENING AND MICROSCOPIC  R/S Workstations
CORRELATIONS o Consists of a glass flow cell into w/c urine
Screening Test Significance sediment is pumped, microscopically
Color Blood examined then flushed from the system
Clarity Hematuria, Hemoglobinuria, Myoglobinuria
Blood RBCs, RBC casts Reporting the Microscopic Examination
CHON Casts, cells
Nitrite Bacteria, WBCs Plus system (LPO) Plus system Average # Average # per
LE WBCs, WBCs casts Rare, few, (HPO) per field field (HPO)
moderate, many/ 1+, Rare, few, (LPO)
Glucose yeast
2+, 3+, 4+ moderate, many/
1+, 2+, 3+, 4+
Specimen Preparation
Mucus thread Bacteria Casts WBC
 Spx should be examined while fresh
o RBCs, WBCs, and hyaline casts disintegrate Yeast/fungi RBC
Squamous Transitional Renal Tubular
rapidly in dilute alkaline urine
Epithelial Cells Epithelial Cells Epithelial Cells
 Refrigeration can cause precipitation of amorphous
urates and phosphates Normal crystals Abnormal
 Midstream clean-catch crystals

Specimen Volume Addis Count (1926)

 10-15 mL, average: 12 mL  1st procedure to standardize the quantitation of formed
 Should be centrifuged in a conical tube elements
 For pediatric px, volume of spx should be indicated on  Used of hemocytometer to count the number of RBCs,
report form so that the physician can correct the WBCs, casts and epithelial cells present in 12-hr spx
results
ROUTINE URINALYSIS CORRELATIONS
Centrifugation:
 5 mins. @ relative centrifugal force (RCF) Microscopic Elements Physical Chemical Exceptions
RBCs Turbidity + Blood Number
Red color + CHON Hemolysis
RCF=1.118 x 10−5 x r ∈cm x RPM 2 WBCs Turbidity + CHON Number
 Calibrator: Tachometer + Nitrite Lysis
+ LE
Sediment Preparation: Epithelial cells Turbidity Number
 0.5 mL and 1.0 mL
Casts + CHON Number
V of urine centrifuged Bacteria Turbidity ↑ pH Number and
 CF =
Sediment volume type
 ‘sediment conc. factor relates to the probability pf + Nitrite
detecting elements present in low quantities and is + WBC
used when quantitating the number of elements Crystals Turbidity pH Number and
present per mL type
 VIGOROUS AGITATION IS NO NO! Color + Bilirubin

Volume of Sediment Examined

o 10-20 fields
o Identification of cast

EXPECTED STAINING RXN OF URINE SEDIMENT CONSTITUENTS

Elements in Urinary Sediments Color of Stained Elements Comments
RBC Pink to purple (neutral)
Pink unstained (acid)
Purple (alkaline) Cytoplasm
WBC Purple Purple granules
Glitter cells Colorless or light blue Pale blue or gray Some exhibit Brownian

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  Sterheimer-Malbin + cells movement
RTE Dark shade of blue-purple Light shade of blue-purple
Bladder tubular epithelial cells Blue-purple Light purple
Squamous epithelial cells Dark shade of orange-purple Light purple or blue

Inclusions and Matrix

Hyaline casts Pale pink or purple Very uniform color
Slightly darker than mucus
thread
Coarse granular inclusion casts Dark purple granules in purple matrix
Finely granular inclusion casts Fine dark purple granules in pale pink or
purple matrix
Waxy casts Pale pink or purple Darker than hyaline
Pale even color
Distinct broken ends
Fat inclusion casts Fat globules unstained in pink matrix Rare
Confirmatory under polarized
light indicates double
refraction
Red cell inclusion casts Pink to orange-red intact cells seen in matrix
Hb casts Orange-red No intact cell
Bacteria Motile: do not stain Motile organisms are not
Non-motile: purple impaired
T. vaginalis Light blue-green Motility is unimpaired in fresh
spx
Mucus Pale pink or blue
Background Pale pink or purple

URINE SEDIMENT STAIN CHARACTERISTICS

STAIN ACTION FUNCTION
Sternheimer-Malbin  Delineates structure Identifies WBCs, epithelial cells and casts
 Consists of crystal violet and safranin  Contrasting colors of nucleus and cytoplasm
O
0.5% sol. of Toluidine blue  Enhances nuclear detail Differentiates WBCs and RTE cells
2% Acetic acid  Lyses RBCs Distinguishes RBCs from WBCs, yeast, oil
 Enhances nuclei of WBCs droplets and crystals
Oil Red O and Sudan III  Stain TAG and neutral fats orange-red Identify free fat droplets and lipid-
 Lipid stains  Do not stain chole containing cells and casts
Gram stain  Differentiates G+ from G- Identifies bacterial casts
Hansel stain  Methylene blue and eosin Y stains eosinophilic Identifies urinary eosinophils
granules
Prussian blue stain  Stains Fe-containing structures Identifies yellow-brown granules of
hemosiderin in cells and casts
URINALYSIS MICROSCOPIC TECHNIQUES
Technique Function
Bright-field routine urinalysis
Phase-contrast Enhances visualization of elements w/ low refractive indices
Polarizing Identification of chole in oval fat bodies, fatty casts and
crystals
Dark-field Identification of T. pallidum
Fluorescence Visualization of naturally fluorescent microorganisms
Interference contrast 3D microscopy image and layer-by-layer imaging

URINE SEDIMENTS
SEDIMENT DESCRIPTION NORMAL CLINICAL SIGNIFICANCE
VALUES
RBC  Crenated -- hypersthenuric urine 0-2/hpf  Dysmorphic
 Ghost cells – hyposthenuric urine o Vary in size
 Most difficult to recognize due to: o Has cellular protrusions
o Lack of structural characteristics o Fragmented
o Variations in size o Associated w/ glomerular
o Close resemblance to others bleeding
 Frequently confused w/:  Damage to glomerular membrane
o Yeasts cells  Vascular injury w/in GUT
 Exhibit budding  Macroscopic hematuria

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 o Oil droplets and Air bubbles o Urine is cloudy w/ red to
 Highly refractile brown color
 Addition of acetic acid to the portion of o Advanced glomerular
sediment will help the identification damage
o Damage to vascular
integrity of UT
 Confirms presence of renal calculi
WBC  Segmenters are usually seen 0-5/hpf
o lyse rapidly in dilute alkaline and begin
to lose nuclear detail
 Glitter Cells
o Due to Brownian movement of granules
w/in larger cells
 NO PATHOLOGIC SIGNIFICANCE
Eosinophils  Hansel’s stain None  Drug-induced interstitial rephritis
 ↑ 1% - pathologic  UTI
 Renal transplant rejection
Mononuclear Cells  Not usually identified in wet prep of urinalysis None  Early stages of renal transplant
 Lymphocytes  Lymphocytes may resemble RBC rejection
 Monocytes  Monocyte, Macrophages, Histiocytes  Pyuria
 Macrophages o Large cells o ↑ urinary WBC
 Histiocytes o May appear vacuolated or contain o Indicates presence of infxn
inclusions or inflammation of GUT
 Pyelonephritis
 cystitis
 SLS
Squamous Epithelial cells  Largest EC  If sides are obscured w/ G. vaginalis,
 Abundant, irregular cytoplasm strong indication of vaginitis
 Prominent nucleus about the size of RBC
 Reported under LPO as rare, few, occasional and
in plusses
 Disintegrates in urine that is not fresh
 Denotes improper collection especially in female
px
Transitional Epithelial Cells  Urothelial cells  Malignancy
 Smaller the SEC  Viral infxn
 Spherical, polyhedral and caudate
 Can absorb water
 Centrally located nuclei
 Originates from the lining of renal pelvis, calyces,
ureters, bladder and upper portion of urethra
 Reported under HPO
 Syncytia
o TEC in clumps
o Due to catheterization
o NO CLINICAL SIGNIFICANCE
RTE cells  Larger than WBCS 0-2/hpf  Tissue destruction
 If in groups of 3-4 – renal damage  Necrosis of Renal tubules
 Reported under HPO o Exposure to heavy metals
 Eccentrically located nuclei o Drug-induced toxicity
o Hb and Mb toxicity
o Hepa B infxn
o Allergic rxn
o Malignant infiltration
Oval Fat Bodies  Bubble Cells None  Lipiduria
 RTE cells w/ absorbed lipids from glomerular  Nephrotic syndrome
filtrate  Severe tubular necrosis
 Seen in conjunction w/ free-floating fat droplets  DM
 Maltese cross formation
 Reported as average # per field
Bacteria  May be present as a result of vaginal, urethral, None  UTI
external genitalia container contamination
 Multiplies rapidly @ room temp
 Reported using HPO
Yeast  Small, refractile oval structures may or may not None  DM
contain bud  Vaginal moniliasis
 May appear branched  Immunocompromised px
 Mycelial forms – severe infxn
 Reported under HPO
 C. albicans
Parasites: T. vaginalis  Pear-shaped flagellate w/ undulating membrane None  If no infxn, possible for fecal
 Rapid, darting movement contamination
 Reported under HPO
 Sexually transmitted

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Spermatozoa  Oval, slightly tapered heads and long flagella-like None  Rare clinical significance except in
tails case of infertility or retrograde
 Reporting will vary in every lab ejaculation where in sperm is
expelled into the bladder instead of
urethra
Mucus  Produced by the glands and epithelial cells 
 Constituent: Uromodulin
 Thread-like structures w/ low refractive index
 Reported under HPO

URINARY CASTS (Cylinduria)

 Provides a microscopic view of conditions w/in the nephron
 Formed w/in the lumens of DCT and CT
 Shape:
o Parallel sides
o Rounded end
o Additional element present in the filtrate
 Perform in LPO
o If cover slip is used, perform along the edges
 LOW REFRACTIVE INDEX – subdued light should be used
 Reported as:
o Average number per 10 lpfs
 Composition
o Formed during:
 Urine-flow stasis
 Acidity
 Presence of Ca and Na
o Cylintroids
 Incomplete cast formation and disintergration
 Cast Cascade:
o Aggregation of uromodulin into individual CHON fibrils attached to RTE
o Interweaving of CHON fibrils to form loose fibrillar network w/ addition of urinary constituents
o Further CHON fibril interweaving to form solid structure
o Detachment of CHON fibrils
o Excretion of casts

CAST DESCRIPTION NORMAL CLINICAL SIGNIFICANCE

VALUES
Hyaline  Precursor of all casts 0-2/lpf  Strenuous exercise
 Voided of other constituents  Dehydration
 Consists entirely of uromodulin  Heat exposure
 Colorless  Acute glomerulonephritis
 Same refractive index with the urine  Pyelonephritis
 Cylindrical forms w/ wrinkled or convoluted  CHF
shapes  Chronic renal dse

RBC  Tightly packed orange-red cells adhering CHON None  Bleeding in GUT w/in the nephron
matrix  Damage to the glomerulus
 Reported under hpo (# per field)

WBC  Mostly composed of neutrophil – granular None  Infxn and inflammation w/in the nephron
o Supravital stain – demonstrate the
nuclei
 Primary marker for distinguishing pyelonephritis
(Upper UTI) from cystitis (lower UTI)
 Reporting: average #/hpf
Bacterial  May resemble granular casts None  Pyelonephritis
o Confirmed thru GS in dried or
cytocentrifuged spx

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 Epithelial Cell  Depends on the EC attached to CHON matrix None  Advanced Tubular Destruction
 Use of phase microscopy for better detection o Leads to urinary stasis w/
disruption of tubular linings
 RTE Casts
o Heavy metal, Chemical and
Drug-induced toxicity
 Viral infxn
Fatty  Seen in conjunction w/ OFB None  Lipiduria
 Highly refractile  Nephrotic syndrome
 Toxic tubular necrosis
 DM
 Crush injuries

Mixed Cellular  Variety of cell seen None  RBC and WBC casts
o Glomerulonephritis
 WBC, RTE and Bacterial Casts
o Pyelonephritis
Granular  Can be – Fine or Coarse (but it doesn’t matter None  Non-pathologic
anyway)  Poor prognosis
 Seen w/ hyaline casts  Strenuous exercise
 Can become waxy casts if allowed to remain in  Urinary stasis
the tubule for extended period of time
 It appears RTE excretes lysosomes in non-
pathologic conditions during normal metabolism
Waxy  End of degeneration of casts None  Chronic renal failure
 High refractive index
 Represent extreme urine stasis
 Fragmented w/ jagged ends and notes on
their sides

Broad  2-6x larges than other casts None  Destruction of tubular wall
 Renal Failure Casts  Tubular necrosis caused by viral hepatitis
 Represents extreme urine stasis
 Most commonly seen: granular or waxy

URINE CRYSTALS  organic

 Formed by precipitation of solutes:  iatrogenic
o Inorganic salts  Alkaline
o Organic cmpds  inorganic
o Medication  Determining the pH of the spx
 Iatrogenic Compounds aids in identification of the type
 Formation factors: of chemicals precipitated
o Temperature o Solute conc.
 Room  Can obscure clinically significant sediment
 Refrigerator (abundant) constituents
o pH  Reported in semi quantitative/lpf
 Affects solubility  Use of polarizing microscopy for better identification
 Acidic o Birefringence
 Ability to polarize light
NORMAL CRYSTALS DESCRIPTION CLINICAL SIGNIFICANCE
Uric acid  pH: acid  Seen in px w/ Leukemia receiving
 Seen in variety of shapes: chemotherapy
o Rhombic  Lesch-Nyhan syndrome
o 4-sided flat planes or whetstones  Gout
o Wedge  Associated w/ increased purine metabolism
o Rosettes
 Yellow-brown in color
 May be colorless + 6 sided shape – similar to cysteine crystals (
UA is highly birefringent than the latter)
Amorphous urate  pH: acid (greater than 5.5)
 Yellow brown in color
 Brick red (after refrigeration)
 May resemble granular casts when in clumps

Calcium oxalate  pH: acid/alkaline  Associated w/ urinary calculi and foods

 CaOx dihydrate high in oxalic acid

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 o A.k.a Weddellite o Tomatoes
o Seen as colorless, octahedral envelope or 2 pyramids o Asparagus
joined together at their bases o Ascorbic acid
 CaOx monohydrate  COM forms – ethylene glycol poisoning in
o A.k.a Wewellite massive amounts
o Oval or dumbbell-shaped o Anti-freeze
Amorphous phosphate  pH: alkaljne
 similar to A. urates (differentiated thru pH)
 White precipitate after refrigeration and does not dissolve on
warming
 Requires acetic acid to dissolve (not advisable thou)

Calcium phosphate  pH: alkaline  Common constituent of renal calculi

 not frequently encountered
 Flat rectangular plates or thin prisms in rosette forms
 Dissolves in dilute acetic acid

Triple phosphate  pH: alkaline  Associated w/ urea-splitting bacteria

 a.k.a Struvite
 Highly birefringent
 Ammonium magnesium phosphate
 Often resembles a ‘coffin lid’
 Feathery appearance – disintegrated form
Ammonium biurate  pH: alkaline  Encountered in presence of urea-splitting
 a.k.a Thorny apples bacteria
 Yellow-brown spicules crystals  In vivo – renal calculi
 When dissolve @60°C, resembles other urate crystals
 Converted to uric acid crystals in addition of acetic acid
Calcium carbonate  pH: alkaline
 small and colorless w/ dumbbell or spherical shapes
 Formation of gas in addition of acetic acid – differentiation from
other amorphous materials

ABNORMAL CRYSTALS DESCRIPTION CLINICAL SIGNIFICANCE

Cystine  Present In px having inherited metabolic disorder – prevents  Tendency to form renal calculi at early age
reabsorption by the renal tubules (Cystinuria)
 Colorless, thick or thin hexagonal plates
 Cyanide-Nitroprusside Test
o Differentiation from UA

Cholesterol  More pronounced after refrigeration  Lipiduria

 Rectangular plates w/ a notch in one or more corners  Nephrotic syndrome
 Seen in conjunction w/ fatty casts and OFB  Excessive tissue breakdown
 Highly birefringent  Obstructed lymphatic flow

Radiographic  Similar appearance to chole crystals

o Differentiated thru other urinalysis results and px
history
 Highly birefringent
 High s.g if refractometer is used

Leucine  Associated w/ liver dse  MSUD

 Yellow-brown spheres w/ concentric circles and radial striations  Oasthouse Urine Dse
 Seen accompanying tyrosine crystals

Tyrosine  Fine colorless to yellow needles  Inherited disorders of amino-acid

 Occurs as clumps or rosettes metabolism
 Associated w/ liver dse – (+) for bilirubin in chem test

Bilirubin  Yellow clumped needles or granules  Hepatic disorders

 (+) bilirubin in chem test  Viral hepatitis

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 Sulfonamide  Px under medication for UTI  Associated w/ tubular damage if crystals are
 Dehydrated px seen in nephron
 May appear as:
o Needles
o Rhombics
o Whetstone
o Sheave of wheat
 Confirmatory: Diazo Rxn

Renal Diseases
Glomerular Disorders

 Results from immunologic disorders forming immune
complexes
 Increased serum IgA are deposited on the glomerular
membranes
 Components of immune system are attracted to the
membranes producing changes and damaging it –
cellular infiltration or proliferation resulting in
thickening of glomerular basement membrane
 Non-immunologic causes:
o Exposure to chemicals and toxins
o Disruption of electrical membrane charges
o Deposition of amyloid material from
systemic disorders
o Basement membrane thickening associated
w/ diabetic nephropathy

Glomerulonephritis
 Sterile, inflammatory process that affects glomerulus and is associated w/ finding of blood, CHON and casts in urine

DISEASES CHARACTERISTICS AND SYMPTOMS URINALYSIS LAB FINDINGS

Acute Poststreptococcal  Respiratory infxn caused by certain strains of group A Streptococcus  Macroscopic Hematuria  Demonstration of + ASO
Glomerulonephritis that contain M protein in cell wall – forms immune complexes w/c  Proteinuria confirms streptococcal
 Marked by sudden are deposited in glomerular membrane  Oliguria origin
onset of symptoms  Inflammatory rxn affects glomerular function  RBC casts
consistent w/ damage  Successful management of secondary complication – hypertension  Dysmorphic RBCs
to glomerular and electrolyte imbalance until the complexes are cleared from the  Hyaline and Granular Casts
membrane blood , results in no permanent kidney damage  WBCs
 Symptoms:
o Fever
o Edema (most noticeably around the eyes)
o Fatigue
o Hypertension
o Oliguria
URINARY o ARTIFACTS
Hematuria DESCRIPTION
o Starch
Elevated BUN  Occurs when cornstarch is the powder used in powdered gloves
 Symptoms usually occurs in childrenand young High refractile
adults spheres w/ dimpled center
Rapidly Progressive  Symptoms:  Can produce maltese cross formation macroscopic hematuria  Same as AGN but become
(Crescentric) o Deposition of immune complexes – results from  Proteinuria more abnormal as the dse
Glomerulonephritis complications such as SLE  RBC casts progresses
 Poorer prognosis o Damage to capillary walls caused by macrophages leading  Elevated CHON levels
leading to renal Oil droplets and Air bubbles  Highly
to – release of cells and plasma refractile
into Bowman’s space  Low GFR
failure o Production of crescentic  Contamination
formations containingby oil immersion  Increased fibrin
macrophages, fibroblasts  Air Bubbles
and polymerized – seen
fibrin if cover slip is used
– causes degradation products
permanent damage to capillary tufts  Cryoglobulins
 Deposition of IgA on the
glomerulus
Pollen grains  Spheres w/ cell wall and concentric circles
Goodpasture Syndrome  Cytotoxic autoAb, Anti-glomerular basement membrane Ab, can  Macroscopic Hematuria  Antiglomerular basement
 An autoimmune appear on glomerular and alveolar membranes after viral respiratory  Proteinuria` membrane Ab
disorder infxn  Presence of RBC casts
 Morphologic changes o autoAb can be detected in px serum
resembling RPG may  Mechanism:
Fibers  Longer and more refractile
be seen o Attachment of autoAb to basement membrane
 Can be mistaken as casts
o Complement activation
o Differentiation is thru polarizing microscopy – fibers
o Production of capillary destruction
 Pulmonary complaints: polarize while the latter is not
o Hemoptysis -- spitting of blood or blood-stained mucus
o Dyspnea – difficulty in breathing
o Development of hematuria

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  If left untreated, progression to:
o Chronic glomerulonephritis
o End-stage renal failure

Wegener Granulomatosis  Binding of autoAb to neutrophils in vascular walls initiate immune  Macroscopic Hematuria  Elevated creatinine and
 Causes granuloma- response resulting in granuloma formation  Proteinuria BUN
producing  Diagnosis:  RBC casts  Demonstration of
inflammation of o Incubation of px serum w/ either ethanol or formalin-fixed antineutrophilic
small blood vessels neutrophis cytoplasmic Ab in px
of kidney and o Examination using immunofixation to detects serum Ab serum
respiratory system attached to neutrophils

(A) Classical ANCA

(B) pANCA
Henoch-Schonlein  Symptoms: (C) Atypical ANCA  May range from mild to  Stool occult blood
Purpura o (D)
Appearance of raised, red patches on skin
Atypical ANCA using heavy proteinuria and
 Occurs primarily on o Blood in sputum and stools confocal L/M hematuria w/ RBC casts
children after upper  Usually respiratory and gastrointestinal infection but if there is renal
respiratory infxn involvement – most serious complication of the disorder

Membranous  Associated disorders:  Microscopic hematuria  Elevated urine CHON

Glomerulonephritis o SLE  Proteinuria excretion
 Pronounced o Sjogren syndrome  Antinuclear Ab
thickening of o Secondary syphilis  Hbs Ag
glomerular basement o Hepa B  FTA-Abs
membrane resulting o Gold and Mercury Tx
from deposition of o Malignancy
IgG immune
 May progress to:
complexes
o Nephrotic syndrome
o Thrombosis – formation of clots in the blood vessels
Membraneproliferative  Type 1:  Hematuria  Decrease serum
Glomerulonephritis o Increased cellularity in sub-endothelial cells of mesangium  Proteinuria complement levels
 Appears associated – interstitial area of Bowman’s capsule causing thickening
w/ autoimmune of capillary walls
disorders, infection o May progress to nephrotic syndrome
and malignancies  Type 2:
o Extremely dense deposits in glomerular basement
membrane
o May experience symptoms of chronic glomerulonephritis
Chronic  Gradually worsening symptoms:  Hematuria  Decreased GFR
Glomerulonephritis o Fatigue  Proteinuria  Increased creatinine and
 Depending on the o Anemia  Glucosuria BUN levels
amount and duration o Hypertension o Result of tubular  Electrolyte imbalance
of the damage to the o Edema dysfunction  eGFR
glomerulus o Oliguria  Cellular and granular casts

IgA Nephropathy  IgA complexes deposits on glomerulus  Macroscopic or Microscopic  Elevated serum IgA
 Aka Berger Dse  Most common cause of glomerulonephritis hematuria
 Frequently seen in children and young adults
 Asymptomatic px have gradual progression to chronic
glomerulonephritis and end-stage renal dse
 Spontaneous recovery from macroscopic hematuria
Nephrotic Syndrome  Acute onset of the disorder can occur in circulatory disruption  Heavy proteinuria  Serum albumin
producing systemic shock that decrease the pressure and flow of  Microscopic hematuria  Cholesterol
blood to the kidney  RTE cells  TAG
 Increased permeability of glomerular membrane due to:  OFB
o Damage to shield of negativity  Fat droplets
o Less tightly connected barrier of podocytes  Fatty and waxy casts
 Hypoalbuminemia can stimulate the increase production of lipids by
the liver
 Lower oncotic pressure in capillaries resulting from decrease plasma
albumin increases fluid loss into interstitial spaces w/c is
accompanied w/ Na retention leading to edema
 Depletion of Ig and coagulation factors leads to px susceptibility to
infxns and coagulation disorders
 May progress to chronic renal failure
Minimal Change Disease  Little cellular change in glomerulus except some damage to  Heavy proteinuria  Serum albumin
 Lipid nephrosis podocytes and shield of negativity  Transient hematuria  Cholesterol
 Associated w/:  Fat droplets  TAG
o Allergic rxn
o Recent immunization
o Possession of HLA-B12
 Responds well to corticosteroids
Focal Segmental  Affects only certain number and areas of glomeruli while the rest  Proteinuria  Drugs of abuse
Glomerulosclerosis remains normal  Microscopic or macroscopic  HIV tests
 IgM and C3 deposits on the glomerulus hematuria
 Associated w/:
o Abuse of heroin and analgesics
o AIDS

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 TUBULAR DISORDERS
DISEASES CHARACTERISTICS AND SYMPTOMS URINALYSIS LAB FINDINGS
Acute Tubular Necrosis  Damage to RTE cells may produce by decreased blood flow that  Microscopic hematuria  Hb
 Primary disorder causes lack of oxygen presentation to the tubules – ischemia  Proteinuria  Hct
associated w/ damage  Presence of toxic substances in urinary filtrate  RTE cells  Cardiac enzymes
to the renal tubules  Disorders causing ischemic ATN:  RTE cell casts
o Shock  Hyaline and Granular casts
 A severe condition that decreases the flow of  Waxy and Broad casts
blood throughout the body
 Cardiac failures, sepsis due to toxigenic
bacteria, anaphylaxis, massive hemorrhage
and contact w/ high-voltage electricity
o Crushing injuries
o Surgical procedures
 Exposure to nephrotic agents can damage and affect the function of
RTE cells such as:
o Aminoglycoside antibiotics
o Antifungal agent
o Amphotericin B
o Cyclosporine
o Radiographic dye
o Ethylene glycol
o Heavy metal
o Toxic mushrooms
 Filtration of large amounts of Hb and Myo are nephrotoxic
Fanconi syndrome  Failure of tubular reabsorption of PCT  Glucosuria  Serum and Urine
 Frequently associated o Dysfunction of the transport of filtered substances across  Possible cysteine crystals electrolytes
w/ tubular tubular membranes  Amino acid
dysfunction o Disruption of cellular energy needed for transport chromatography
o Changes in tubular membrane permeability
 Can be inherited in association w/:
o Cystinosis and Hartnup Dse
o Acquired thru exposure to toxic agents – heavy metals and
outdated tetracycline
o Complication of multiple myeloma and renal transplant
Alport syndrome  Inherited disorder of collagen production affecting the glomerular  Macroscopic and
basement membrane microscopic hematuria
 Can be inherited as sex-linked or autosomal genetic disorder (males younger than 6 years
 Males inheriting X-linked gene are more severely affected than
females inheriting autosomal gene
 Abnormalities in hearing and vision may also develop
 Lamellated glomerular basement membrane w/ areas of thinning
Uromodulin-Associated  Uromodulin – only CHON produced in PCT and DCT  RTE cells  Increased serum UA
Kidney Dse  Autosomal mutation in the gene that produces uromodulin producing gout as early as
 Decreases in production of normal uromodulin that is replaced by the teenage
abnormal form
 Mechanism:
o Abnormal uromodulin is still produced by tubular cells
o Accumulation will lead to their destruction
o Destruction w/c leads to the need for renal monitoring and
eventual renal transplant
Diabetic nephropathy  Most common cause of end-stage renal disease
 Damage to glomerular membrane as a result of:
o Glomerular membrane thickening
o Increased proliferation of mesangial cells
o Increased deposition of cellular and non-cellular material
w/in glomerular matrix resulting in accumulation of solid
substances around capillary tuffs
 Deposition of glycosylated CHON resulting from poorly controlled
blood glucose levels
 May develop sclerosis
 Monitoring for the presence of microalbuminuria to detect the onset
Nephrogenic Diabetes  Disrupted ADH action either by inability of renal tubules to respond to  Low s.g
Insipidus ADH or failure production of ADH  Pale yellow color
 Can be inherited as sex-linked recessive gene or acquired medication –  False-negative for chemical
lithium and Amphotericin B tests
 Seen as complication of polycystic kidney disease and sickle cell
anemia

Renal Glycosuria  Exhibits a generalized failure to reabsorb substances from glomerular  Glucosuria  Blood glucose
filtrate, renal glucosuria affects only the reabsorption of glucose
 Inherited autosomal recessive trait
 Number of glucose transporters in the tubules is decreased
 Affinity of transporters for glucose is decreased
 Increased urine glucose conc. w/ normal blood glucose conc.

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 INTERSTITIAL DISORDERS
DISEASES CHARACTERISTICS AND SYMPTOMS URINALYSIS LAB FINDINGS
Acute Pyelonephritis  Infxn of upper UTI – pyelonephritis  Leukocyturia  Urine culture
 Result of ascending movement of bacteria from lower UTI into renal  Bacteriuria
tubules and interstitium  WBC casts
 Incomplete emptying of bladder during urination  Bacterial casts
 S/S:  Microscopic hematuria
o Obstruction to renal calculi  Proteinuria
o Pregnancy
o Vesicourethral reflux
 Can be resolved w/out permanent damage to tubules
Chronic Pyelonephritis  Can result in permanent damage to renal tubules  Leukocyturia  Urine culture
 Can progress to chronic renal failure  Bacteriuria  BUN
 Cause: Congenital urinary structural defects producing reflux  WBC casts  Creatinine
nephropathy  Bacterial casts  eGFR
 Often diagnosed to children – asymptomatic at first but can be  Granular, Waxy, Broad casts
observed until onset of tubular damage  Hematuria
 Proteinuria
Acute Interstitial  Marked inflammation of renal interstitium followed by inflammation  Hematuria  Urine eosinophils
Nephritis of renal tubules  Proteinuria  BUN
 S/S:  Leukocyturia  Creatinine
o Oliguria  WBC casts  eGFR
o Edema
o Decreased GFR
o Fever and presence of skin rash – initial symptoms
 Allergic rxn to medication in renal interstitium caused by binding to
interstitial CHON
 Symptoms can be seen after 2 weeks following administration of
medications
 Medications such as:
o Penicillin, Methicillin, Ampicillin, Cephalosporins
o Sulfonamides, NSAIDs
o Thiazide diuretics
 Administering of steroids can reverse this condition
 Renal dialysis are also suggestive to treatment
Renal Failure  Progression from original disease to chronic renal failure or end-stage  Proteinuria
renal disease  Renal glycosuria
 Marked by decrease GFR, rising serum BUN and Creatinine levels –
azotemia, electrolyte imbalance, production of isosthenuric urine,
abundance of granular, waxy and broad casts – Telescoped urine
sediment
Acute Renal Failure  Reversible  RTE cells
 Exhibits sudden loss of renal function  RBC
 S/S:  WBC casts
o Decrease GFR  Presence of urothelial cells
o Oliguria
o Edema and Azotemia
Renal Lithiasis  Formation of kidney stones in calyces, pelvis, ureters and bladder 
 Large, staghorn calculi resembling the shape of pelvis
 Formed in an environment same w/ crystals:
o pH
o chemical concentration
o urinary stasis
 Lithotripsy
o High-energy shock waves to destroy the stone into smaller
pieces in order to pass thru ureters
 X-ray crystallography – more comprehensive analysis
 Composition:
o Calcium oxalate or Calcium phosphate
o Struvite
o UA and Cystine crystals
 Can produce pain radiating from lower back to the legs

URINE SCREENING FOR METABOLIC DISORDERS

Metabolic disorders – caused by disruption of normal metabolism of the substance which leads it to increase in the plasma (overflow)
TYPES:

1. RENAL TYPE- malfunction of renal absorption

2. HEREDITARY (OVERFLOW)- loss of enzyme/s for metabolism (Inborn errors of metabolism)
o Inborn errors of metabolism are detected and monitored through traditional means of urine testing
o Screening methods for IEMs are more sensitive and can detect as many as 30 disorders in just one testing (NEWBORN
SCREENING TEST)
o Build-up of unmetabolized substances in the blood and urine is lethal to the baby, therefore, immediate detection is
necessary
o Tandem Mass Spectrophotometry(MS/MS)- method for NBS

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 PHENYLALANINE-TYROSINE DISORDERS
1. Phenylketonuria (PKU)
2. Tyrosyluria
3. Melanuria
4. Alkaptonuria
BRANCHED CHAIN AMINO ACID DISORDERS
5. MSUD
6. Organic Acidemias
TRYPTOPHAN DISORDERS
7. Indicanuria
8. 5-Hydroxyindoleaceticacid
CYSTINE DISORDERS
9. Cystinuria
10. Cystinosis

METABOLIC ETIOLOGY CLINICAL COURSE METHOD OF ADDITIONAL INFORMATION

DISORDER
PHENYLKETONUR Disrupted conversion of PLA to tyrosine
IA
Inheritance of the gene for the production
of PLA hydroxylase
TYROSYLURIA Underdevelopment of the liver function
Severe liver diseases Urinary overflow of
tyrosine
Type 1- fumarylacetoacetate hydrolase
Type 2- tyrosine aminotransferase
TYPE 3- p- hydroxyphenylpyruvic
acid dioxygenase
Build of PLA causes mental
retardation
Tyrosine and leucine
crystals might be seen
during urine microscopy
Type 1- renal tubular
disorders and liver failure
Type 2 - corneal erosion,
lesions in the palms, fingers
and soles
Type 3 - mental retardation
DETECTION
New Born Screening (24
hours after delivery)
Ferric Chloride Test – blue
green (phenylpyruvic acid)
New Born Screening Urine
Nitroso-Naphthol Test –
Orange Red color
Ferric Chloride Test –
Transient Green
Avoidance of diet rich in
phenylalaine (e.g milk)
 As the child matures, alternative
pathways of Phenylalanine
metabolism develop, hence less
Phenylalanine are unmetabolized,
dietary restrictions are eased
 Appearance of phenylpyruvic acid in
the urine is after 2-6 weeks
 Transitory tyrosinemia- liver
function is not well developed in
infants
 Crystallization of tyrosine in the
tissue cells

MELANURIA Malignant Melanoma  Albinism (deficient
production)
 Increased urinary
melanin makes a dark
urine upon exposure to
air
SODIUM  Increased urinary melanin maybe
NITROFERRICYANIDE – caused by increased proliferation
Red color of melanin producing cells
(malignant melanoma)
 5,6-dihyroxyindole (precursor of
FeCl3 test: Gray or Black ppt
melanin) in the urine oxidized to
melanogen then melanin

ALKAPTONURIA  Failure to inherit the gene for  Accumulation of HA
production of homogentisic acid in blood, tissues and
oxidase enzyme urine
 Red Disposable
Diaper Syndrome –
brown or black
stained cloth diapers
 Alkaline urine darkens  Deposition of HA in the cartilage
at room temperature may lead to:
o Arthritis
SILVER NITRATE TEST – o Liver and Cardiac
Black color disorders
FeCl3 Test: Transient Deep
Blue color

Paper and Thin Layer

chromatography
(quantification)

MAPLE SYRUP  Autosomal recessive  Failure to thrive Maple syrup urine odor  Accumulation of one or more early
URINE DISEASE trait after 1 week degradation products,
 Presence of Leucine, Isoleucine,  Severe mental 2,4-  Ketonuria in newborn
Valine in blood and urine retardation DINITROPHENYLHYDRA  Odor- ketone accumulation
 Failure to inherit the enzyme  Death ZINE TEST -- Yellow  Detection on or before the 11th day,
needed for oxidative precipitate or turbidity dietary regulation and monitoring
decarboxylation can control the disorder

ORGANIC Isovaleric Acidemia  Vomiting Sweaty feet urine odor Accumulatiuon of isovalerylglycine
ACIDEMIAS *Deficiency of  Metabolic causes the odor
Isovaleryl Coenzyme A Acidosis Newborn Screening
 Hypoglycemia Test
Propionic and  Ketonuria
Methylmalonic  Increased Serum
 No conversion of isoleucine, valine, ammonia
threonine and methionine to
Succinyl coenzyme A
INDICANURIA Increase in converted indole BLUE DIAPER Indigo blue colored urine  Increased urinary indican and 5-

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 SYNDROME
Causes: Urine is colorless but turns
 Intestinal disorders to indigo blue when
(eg obstruction) oxidized
 Abnormal bacteria Blue discoloration in
 Malabsorption infant’s diaper
when exposed to air hydroxyindoleacetic acid (5HIAA)
 Normally, tryptophan is reabsorbed
FeCl3 Test -- Violet with or converted to indole then indican
chloroform by intestinal bacteria and excreted in
the
feces

FANCONI’S SYNDROME HARTNUP’S

 If indole is in excess,it is
HARTNUP’S DISEASE recirculated through the liver and is
converted to indican and excreted in
the urine

Normalize when the cause is corrected

ARGENTAFFINO Carcinoid tumors of argentaffin SILVER NITROPRUSSIDE
MA (enterochromaffin) TEST
 Purple to black
FeCl3 test -- Blue Green
HPLC with
FLOURESCENCE
CYSTINURIA Inability of the renal tubule to reabsorb May lead to formation of Cystine crystal in urine
cysteine (inherited) renal calculi
CYANIDE-
NITROPRUSSIDE TEST--
Red Purple Color
 Serotonin is produced from
tryptophan by argentaffin cells in
the intestines and carried in the
circulation by platelets
 Almost used up and small
degradation product 5HIAA is
secreted in the urine
 Tumors of argentaffin cells lead to
excess serotonin and excess
5HIAA (normal 2-8 mg, 25 mg/24
hours tumor)
 Increased cysteine in the urine

CYSTINOSIS Nephropathic Crystalline deposits on S&S

defect on the lysosomal membrane not cornea, bone marrow,
allowing the release of cystine into the lymph nodes, internal
cells for metabolism organs
Non-nephropathic
Fanconi’s Syndrome
HOMOCYSTINURI Defects in the metabolism of methionine  Failure to thrive
A and homocystine  Cataract
 Mental
Retardation
 Death
 Lack of urinary concentration
 Generalized aminociduruia
Newborn Screening
SILVER NITROPRUSSIDE
TEST
 Red-purple

PORPHYRIN Lead Poisoning Photosensitivity Port Wine Urine Products of heme metabolism caused by
DISORDERS breakdown of RBC ,
Excess alcohol intake Neurologic Ehrlich’s Reaction Hepatic Malfunctions and Exposure to
Toxic Agents
Fe deficiency Psychiatric Fluorescence Technique 3 porphyrins: Uroporphyrin, ALA and
Renal disease porphobilinogen are soluble and appear in
urine
Chronic liver disease
Coproporphyrin less soluble

Protoporphyrin not soluble and not seen

in urine

Blockage of the pathway, results to

accumulation of product formed before
the interruption
MUCOPOLYSACCH Inability to metabolize Hurler’s Syndrome Acid albumin  Products found in urine are dermatan
A mucopolysaccharides results to *Accumulation in the cornea  white turbidity sulphate, keratin sulphate, heparin
RIDE DISORDERS accumulation of polysaccharides to *Abnormal skeletal sulphate
the lysosomes of connective tissue structures  Cetyltrimethylammonium bromide
cells and increased excretion in the *Mental retardation  CTAB is read after 5 mins
CTAB turbidity test
urine  Acid albumin is read after 30 mins
 white turbidity
Hunter’s  Turbidity Scale: 0-4

Metachromatic staining spot

Sanfilippo’s *Mental test
retardation
PURINE Lesch Nyhan Disease  Excessive Orange sands in
DISORDERS No inherited gene for the production of accumulation of uric diapers
hypoxanthine guanine phosphoribosyl acid crystals in the
transferase body
 Motor defects, gout,
renal calculi, mental
retardation

CHO DISORDERS  GALACTUSORIA CLINITEST Galactose 1 phosphate urydyl transfearse

• Deficiency in GALT
• Galactokinase Pregnancy and lactation
• UDP-galactose4-

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 epimerase
 LACTOSURIA Ingestion of fruit
 FRUCTOSURIA

WATSON SCHWARTZ DIFFERENTIATION TEST

 For differentiating urobilinogen and porphobilinogen and other ehrlich compounds o Urobilinogen is soluble to butanol and
chloroform o Porphobilinogen is not soluble to butanol and chloroform o Other Ehrlich compounds: soluble in butanol but not soluble
in chloroform
Urobilinogen Porphobilinogen Other Ehrlich-
Reactive Substances

Chloroform
Extraction
Top Layer: Urine
Bottom Layer: Colorless Red Red
Chloroform Red Colorless Colorless

Butanol Extraction
Top Layer: Butanol Red Colorless Red
Bottom Layer: Urine Colorless Red Colorless

HOESCH TEST (+): red color

 Rapid screening test for urine porphobilinogen
 Ehrlich’s reagent dissolved in 6M HCl (2 mg/dL)

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