MICROSCOPIC EXAMINATION OF URINE Commercial Systems

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

Specimen Volume Addis Count (1926)

 10-15 mL, average: 12 mL
 Should be centrifuged in a conical tube
 For pediatric px, volume of spx should be
indicated on report form so that the
physician can correct the results
 1st procedure to standardize the quantitation
of formed elements
 Used of hemocytometer to count the
number of RBCs, WBCs, casts and epithelial
cells present in 12-hr spx

Centrifugation: ROUTINE URINALYSIS CORRELATIONS

 5 mins. @ relative centrifugal force (RCF)
Microscopic Elements Physical Chemical Exceptions
𝑅𝐶𝐹 = 1.118 𝑥 10−5
𝑥 𝑟 𝑖𝑛 𝑐𝑚 𝑥 𝑅𝑃𝑀2 RBCs Turbidity + Blood Number
 Calibrator: Tachometer Red + CHON Hemolysis
color
Sediment Preparation: WBCs Turbidity + CHON Number
 0.5 mL and 1.0 mL + Nitrite Lysis
𝑉 𝑜𝑓 𝑢𝑟𝑖𝑛𝑒 𝑐𝑒𝑛𝑡𝑟𝑖𝑓𝑢𝑔𝑒𝑑 + LE
 𝐶𝐹 =
𝑆𝑒𝑑𝑖𝑚𝑒𝑛𝑡 𝑣𝑜𝑙𝑢𝑚𝑒 Epithelial cells Turbidity Number
 ‘sediment conc. factor relates to the
Casts + CHON Number
probability pf detecting elements present in
Bacteria Turbidity ↑ pH Number and
low quantities and is used when quantitating
type
the number of elements present per mL
+ Nitrite
 VIGOROUS AGITATION IS NO NO!
+ WBC
Crystals Turbidity pH Number and
Volume of Sediment Examined
 20µL (0.02 mL) covered by a 22 x 22 mm glass type
cover slip Color + Bilirubin
 LPO
o 10 fields
o Casts and composition of sediment
 HPO
o 10-20 fields
o Identification of cast

[A]
 URINE SEDIMENT STAIN CHARACTERISTICS
STAIN ACTION FUNCTION
Sternheimer-Malbin  Delineates structure Identifies WBCs, epithelial cells and
 Consists of crystal violet and  Contrasting colors of nucleus and cytoplasm casts
safranin 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,
 Enhances nuclei of WBCs oil 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 Identifies urinary eosinophils
eosinophilic granules
Prussian blue stain  Stains Fe-containing structures Identifies yellow-brown granules of
hemosiderin in cells and casts

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
 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

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

[A]
 URINE SEDIMENTS
SEDIMENT DESCRIPTION NORMAL VALUES CLINICAL SIGNIFICANCE
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/
o Close resemblance to others glomerular bleeding
 Frequently confused w/:  Damage to glomerular
o Yeasts cells membrane
 Exhibit budding  Vascular injury w/in GUT
o Oil droplets and Air bubbles  Macroscopic hematuria
 Highly refractile o Urine is cloudy w/ red
 Addition of acetic acid to the portion of to brown color
sediment will help the identification o Advanced glomerular
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
 ↑ 1% - pathologic rephritis
 UTI
 Renal transplant rejection
Mononuclear Cells  Not usually identified in wet prep of None  Early stages of renal transplant
 Lymphocytes urinalysis rejection
 Monocytes  Lymphocytes may resemble RBC  Pyuria
 Macrophages  Monocyte, Macrophages, Histiocytes o ↑ urinary WBC
 Histiocytes o Large cells o Indicates presence of
o May appear vacuolated or infxn or inflammation
contain inclusions of GUT
 Pyelonephritis
 cystitis
 SLS
Squamous Epithelial cells  Largest EC  If sides are obscured w/ G.
 Abundant, irregular cytoplasm vaginalis, strong indication of
 Prominent nucleus about the size of RBC vaginitis
 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
 Eccentrically located nuclei metals
o Drug-induced toxicity
o Hb and Mb toxicity
o Hepa B infxn
o Allergic rxn
o Malignant infiltration

[A]
 Oval Fat Bodies  Bubble Cells None  Lipiduria
 RTE cells w/ absorbed lipids from  Nephrotic syndrome
glomerular filtrate  Severe tubular necrosis
 Seen in conjunction w/ free-floating fat  DM
droplets
 Maltese cross formation
 Reported as average # per field
Bacteria  May be present as a result of vaginal, None  UTI
urethral, external genitalia container
contamination
 Multiplies rapidly @ room temp
 Reported using HPO
Yeast  Small, refractile oval structures may or None  DM
may not 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 None  If no infxn, possible for fecal
membrane contamination
 Rapid, darting movement
 Reported under HPO
 Sexually transmitted
Spermatozoa  Oval, slightly tapered heads and long None  Rare clinical significance
flagella-like tails except in case of infertility or
 Reporting will vary in every lab retrograde 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

[A]
 CAST DESCRIPTION NORMAL VALUES CLINICAL SIGNIFICANCE
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  CHF
convoluted shapes  Chronic renal dse

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

WBC  Mostly composed of neutrophil – granular None  Infxn and inflammation w/in
o Supravital stain – demonstrate the nephron
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

Epithelial Cell  Depends on the EC attached to CHON None  Advanced Tubular Destruction
matrix o Leads to urinary stasis
 Use of phase microscopy for better w/ disruption of tubular
detection 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 None  Non-pathologic
matter anyway)  Poor prognosis
 Seen w/ hyaline casts  Strenuous exercise
 Can become waxy casts if allowed to  Urinary stasis
remain in 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
 Represents extreme urine stasis hepatitis
 Most commonly seen: granular or waxy

[A]
 URINE CRYSTALS  Alkaline
 Formed by precipitation of solutes:  inorganic
o Inorganic salts  Determining the pH of the
o Organic cmpds spx aids in identification of
o Medication the type of chemicals
 Iatrogenic Compounds precipitated
 Formation factors: o Solute conc.
o Temperature  Can obscure clinically significant sediment
 Room constituents
 Refrigerator (abundant)  Reported in semi quantitative/lpf
o pH  Use of polarizing microscopy for better
 Affects solubility identification
 Acidic o Birefringence
 organic  Ability to polarize light
 iatrogenic

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
o Rosettes metabolism
 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

 CaOx dihydrate foods high in oxalic acid
o A.k.a Weddellite o Tomatoes
o Seen as colorless, octahedral envelope or 2 o Asparagus
pyramids joined together at their bases o Ascorbic acid
 CaOx monohydrate  COM forms – ethylene glycol
o A.k.a Wewellite poisoning in 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

 a.k.a Struvite bacteria
 Highly birefringent
 Ammonium magnesium phosphate
 Often resembles a ‘coffin lid’
 Feathery appearance – disintegrated form
Ammonium biurate  pH: alkaline  Encountered in presence of urea-
 a.k.a Thorny apples splitting 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

[A]
ABNORMAL CRYSTALS DESCRIPTION CLINICAL SIGNIFICANCE
Cystine  Present In px having inherited metabolic disorder –  Tendency to form renal calculi at
prevents reabsorption by the renal tubules (Cystinuria) early age
 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  Oasthouse Urine Dse
striations
 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

Sulfonamide  Px under medication for UTI  Associated w/ tubular damage if

 Dehydrated px crystals are seen in nephron
 May appear as:
o Needles
o Rhombics
o Whetstone
o Sheave of wheat
 Confirmatory: Diazo Rxn

URINARY ARTIFACTS DESCRIPTION

Starch  Occurs when cornstarch is the powder used in
powdered gloves
 High refractile spheres w/ dimpled center
 Can produce maltese cross formation

Oil droplets and Air bubbles  Highly refractile

 Contamination by oil immersion
 Air Bubbles – seen if cover slip is used

Pollen grains  Spheres w/ cell wall and concentric circles

Fibers  Longer and more refractile

 Can be mistaken as casts
o Differentiation is thru polarizing microscopy –
fibers polarize while the latter is not

[A]
 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  Respiratory infxn caused by certain strains of group A  Macroscopic  Demonstration of +
Poststreptococcal Streptococcus that contain M protein in cell wall – forms Hematuria ASO confirms
Glomerulonephritis immune complexes w/c are deposited in glomerular  Proteinuria streptococcal origin
 Marked by membrane  Oliguria
sudden onset of  Inflammatory rxn affects glomerular function  RBC casts
symptoms  Successful management of secondary complication –  Dysmorphic RBCs
consistent w/ hypertension and electrolyte imbalance until the  Hyaline and Granular
damage to complexes are cleared from the blood , results in no Casts
glomerular permanent kidney damage  WBCs
membrane  Symptoms:
o Fever
o Edema (most noticeably around the eyes)
o Fatigue
o Hypertension
o Oliguria
o Hematuria
o Elevated BUN
 Symptoms usually occurs in children and young adults
Rapidly Progressive  Symptoms:  macroscopic  Same as AGN but
(Crescentric) o Deposition of immune complexes – results from hematuria become more
Glomerulonephritis complications such as SLE  Proteinuria abnormal as the dse
 Poorer prognosis o Damage to capillary walls caused by  RBC casts progresses
leading to renal macrophages leading to – release of cells and  Elevated CHON levels
failure plasma into Bowman’s space  Low GFR
o Production of crescentic formations containing  Increased fibrin
macrophages, fibroblasts and polymerized fibrin degradation products
– causes permanent damage to capillary tufts  Cryoglobulins
 Deposition of IgA on
the glomerulus

Goodpasture  Cytotoxic autoAb, Anti-glomerular basement membrane  Macroscopic  Antiglomerular

Syndrome Ab, can appear on glomerular and alveolar membranes Hematuria basement membrane
 An autoimmune after viral respiratory infxn  Proteinuria` Ab
disorder o autoAb can be detected in px serum  Presence of RBC casts
 Morphologic  Mechanism:
changes o Attachment of autoAb to basement membrane
resembling RPG o Complement activation
may be seen o Production of capillary destruction
 Pulmonary complaints:
o Hemoptysis -- spitting of blood or blood-stained
mucus
o Dyspnea – difficulty in breathing
o Development of hematuria
 If left untreated, progression to:
o Chronic glomerulonephritis
o End-stage renal failure

Wegener  Binding of autoAb to neutrophils in vascular walls initiate  Macroscopic  Elevated creatinine
Granulomatosis immune response resulting in granuloma formation Hematuria and BUN
 Causes  Diagnosis:  Proteinuria  Demonstration of
granuloma- o Incubation of px serum w/ either ethanol or  RBC casts antineutrophilic
producing formalin-fixed neutrophis cytoplasmic Ab in px
inflammation of o Examination using immunofixation to detects serum
small blood serum Ab attached to neutrophils
vessels of kidney
and respiratory
(A) Classical
system
ANCA
(B) pANCA
(C) Atypical
ANCA
(D) Atypical
ANCA using [A]
confocal
L/M
 Henoch-Schonlein  Symptoms:  May range from mild to  Stool occult blood
Purpura o Appearance of raised, red patches on skin heavy proteinuria and
 Occurs primarily o Blood in sputum and stools hematuria w/ RBC casts
on children after  Usually respiratory and gastrointestinal infection but if there
upper respiratory is renal involvement – most serious complication of the
infxn 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 o Hepa B  FTA-Abs
basement o Gold and Mercury Tx
membrane o Malignancy
resulting from  May progress to:
deposition of IgG o Nephrotic syndrome
immune o Thrombosis – formation of clots in the blood
complexes vessels
Membraneproliferative  Type 1:  Hematuria  Decrease serum
Glomerulonephritis o Increased cellularity in sub-endothelial cells of  Proteinuria complement levels
 Appears mesangium – interstitial area of Bowman’s
associated w/ capsule causing thickening of capillary walls
autoimmune o May progress to nephrotic syndrome
disorders,  Type 2:
infection and o Extremely dense deposits in glomerular
malignancies basement membrane
o May experience symptoms of chronic
glomerulonephritis
Chronic  Gradually worsening symptoms:  Hematuria  Decreased GFR
Glomerulonephritis o Fatigue  Proteinuria  Increased creatinine
 Depending on o Anemia  Glucosuria and BUN levels
the amount and o Hypertension o Result of  Electrolyte imbalance
duration of the o Edema tubular  eGFR
damage to the o Oliguria dysfunction
glomerulus  Cellular and granular
casts

IgA Nephropathy  IgA complexes deposits on glomerulus  Macroscopic or  Elevated serum IgA
 Aka Berger Dse  Most common cause of glomerulonephritis Microscopic 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  Heavy proteinuria  Serum albumin
disruption producing systemic shock that decrease the  Microscopic hematuria  Cholesterol
pressure and flow of 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  Little cellular change in glomerulus except some damage  Heavy proteinuria  Serum albumin
Disease to podocytes and shield of negativity  Transient hematuria  Cholesterol
 Lipid nephrosis  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  Proteinuria  Drugs of abuse
Glomerulosclerosis the rest remains normal  Microscopic or  HIV tests
 IgM and C3 deposits on the glomerulus macroscopic
 Associated w/: hematuria
o Abuse of heroin and analgesics
o AIDS

[A]
 TUBULAR DISORDERS
DISEASES CHARACTERISTICS AND SYMPTOMS URINALYSIS LAB FINDINGS
Acute Tubular  Damage to RTE cells may produce by decreased blood  Microscopic hematuria  Hb
Necrosis flow that causes lack of oxygen presentation to the  Proteinuria  Hct
 Primary disorder tubules – ischemia  RTE cells  Cardiac enzymes
associated w/  Presence of toxic substances in urinary filtrate  RTE cell casts
damage to the  Disorders causing ischemic ATN:  Hyaline and Granular
renal tubules o Shock casts
 A severe condition that decreases the  Waxy and Broad casts
flow of 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 o Dysfunction of the transport of filtered substances  Possible cysteine electrolytes
associated w/ across tubular membranes crystals  Amino acid
tubular o Disruption of cellular energy needed for transport chromatography
dysfunction 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  Macroscopic and
glomerular basement membrane microscopic hematuria
 Can be inherited as sex-linked or autosomal genetic (males younger than 6
disorder 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-  Uromodulin – only CHON produced in PCT and DCT  RTE cells  Increased serum UA
Associated Kidney  Autosomal mutation in the gene that produces producing gout as
Dse uromodulin early as teenage
 Decreases in production of normal uromodulin that is
replaced by the 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  Low s.g
Insipidus respond to ADH or failure production of ADH  Pale yellow color
 Can be inherited as sex-linked recessive gene or acquired  False-negative for
medication – lithium and Amphotericin B chemical tests
 Seen as complication of polycystic kidney disease and
sickle cell anemia

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 Renal Glycosuria  Exhibits a generalized failure to reabsorb substances from  Glucosuria  Blood glucose
glomerular 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.

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  Bacteriuria
into renal 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  WBC casts  Creatinine
reflux nephropathy  Bacterial casts  eGFR
 Often diagnosed to children – asymptomatic at first but  Granular, Waxy, Broad
can be observed until onset of tubular damage casts
 Hematuria
 Proteinuria
Acute Interstitial  Marked inflammation of renal interstitium followed by  Hematuria  Urine eosinophils
Nephritis inflammation 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  Proteinuria
end-stage 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
o Oliguria cells
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

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 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

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 DISORDER ETIOLOGY CLINICAL COURSE METHOD OF DETECTION ADDITIONAL INFORMATION

PHENYLKETONURIA Disrupted conversion of
PLA to tyrosine
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
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
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

Type 2- tyrosine Type 3 - mental retardation

aminotransferase

TYPE 3- p-
hydroxyphenylpyruvic
acid dioxygenase

MELANURIA Malignant Melanoma  Albinism (deficient SODIUM  Increased urinary melanin

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

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 ALKAPTONURIA  Failure to inherit the  Accumulation of HA  Alkaline urine  Deposition of HA in the
gene for production of in blood, tissues and darkens at room cartilage may lead to:
homogentisic acid urine temperature o Arthritis
oxidase enzyme  Red Disposable o Liver and
Diaper Syndrome – SILVER NITRATE TEST – Cardiac
brown or black Black color disorders
stained cloth diapers
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
URINE DISEASE trait after 1 week early degradation products,
 Presence of Leucine,  Severe mental 2,4-  Ketonuria in newborn
Isoleucine, Valine in retardation DINITROPHENYLHYDRAZINE  Odor- ketone accumulation
blood and urine  Death TEST -- Yellow precipitate
 Detection on or before the
 Failure to inherit the or turbidity
11th day, dietary regulation
enzyme needed for and monitoring can control
oxidative the disorder
decarboxylation
ORGANIC Isovaleric Acidemia  Vomiting Sweaty feet urine odor Accumulatiuon of
ACIDEMIAS *Deficiency of  Metabolic isovalerylglycine causes the odor
Isovaleryl Coenzyme A Acidosis Newborn Screening
 Hypoglycemia Test
Propionic and  Ketonuria
Methylmalonic  Increased Serum
 No conversion of ammonia
isoleucine, valine,
threonine and
methionine to Succinyl
coenzyme A
INDICANURIA Increase in converted BLUE DIAPER SYNDROME Indigo blue colored urine  Increased urinary indican
indole Urine is colorless but turns when exposed to air and 5- hydroxyindoleacetic
to indigo blue when acid (5HIAA)
Causes: oxidized FeCl3 Test -- Violet with  Normally, tryptophan is
 Intestinal disorders Blue discoloration in chloroform reabsorbed or converted to
(eg obstruction) infant’s diaper indole then indican by
 Abnormal intestinal bacteria and
bacteria FANCONI’S SYNDROME excreted in the
 Malabsorption feces
HARTNUP’S DISEASE
HARTNUP’S
 If indole is in excess,it is
recirculated through the liver
and is converted to indican
and excreted in the urine

Normalize when the cause is

corrected
ARGENTAFFINOMA Carcinoid tumors of SILVER NITROPRUSSIDE TEST  Serotonin is produced from
argentaffin  Purple to black tryptophan by argentaffin
(enterochromaffin) cells in the intestines and
FeCl3 test -- Blue Green carried in the circulation by
platelets
HPLC with FLOURESCENCE  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)
CYSTINURIA Inability of the renal tubule May lead to formation of Cystine crystal in urine  Increased cysteine in the
to reabsorb cysteine renal calculi urine
(inherited) CYANIDE- NITROPRUSSIDE
TEST-- Red Purple Color

CYSTINOSIS Nephropathic Crystalline deposits on S&S

defect on the lysosomal
membrane not allowing
the release of cystine into
the cells for metabolism
Non-nephropathic
cornea, bone marrow,  Lack of urinary concentration
lymph nodes, internal  Generalized aminociduruia
organs
Fanconi’s Syndrome

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 HOMOCYSTINURIA Defects in the metabolism  Failure to thrive Newborn Screening
of methionine and  Cataract
homocystine  Mental SILVER NITROPRUSSIDE TEST
Retardation  Red-purple
 Death

PORPHYRIN DISORDERS Lead Poisoning o Photosensitivity Port Wine Urine Products of heme metabolism
o caused by breakdown of RBC ,
Excess alcohol intake o Neurologic Ehrlich’s Reaction Hepatic Malfunctions and
o Exposure to Toxic Agents
Fe deficiency o Psychiatric Fluorescence Technique
3 porphyrins: Uroporphyrin, ALA
and porphobilinogen are soluble
Renal disease
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
MUCOPOLYSACCHA Inability to metabolize Hurler’s Syndrome Acid albumin  Products found in urine are
RIDE DISORDERS mucopolysaccharides *Accumulation in the  white turbidity dermatan sulphate, keratin
results to cornea sulphate, heparin sulphate
accumulation of *Abnormal skeletal  Cetyltrimethylammonium
polysaccharides to structures CTAB turbidity test bromide
the lysosomes of *Mental retardation  white turbidity  CTAB is read after 5 mins
connective tissue cells o  Acid albumin is read after 30
and increased o Hunter’s Metachromatic staining
mins
excretion in the urine o spot test
 Turbidity Scale: 0-4
o Sanfilippo’s *Mental
retardation
PURINE DISORDERS Lesch Nyhan Disease  Excessive Orange sands in
No inherited gene for the accumulation of uric diapers
production of acid crystals in the
hypoxanthine guanine body
phosphoribosyl transferase  Motor defects, gout,
renal calculi, mental
retardation

CHO DISORDERS  GALACTUSORIA CLINITEST Galactose 1 phosphate urydyl

• Deficiency in transfearse
GALT
Pregnancy and lactation
• Galactokinase
• UDP-
Ingestion of fruit
galactose4-
epimerase
 LACTOSURIA
 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 Colorless Red Red
Bottom Layer: Red Colorless Colorless
Chloroform

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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