Dr. Sachin Verma MD, FICM, FCCS, ICFCDr. Sachin Verma MD, FICM, FCCS, ICFC

Fellowship in Intensive Care MedicineFellowship in Intensive Care Medicine

Infection Control Fellows Course Infection Control Fellows Course

Consultant Internal Medicine and Critical CareConsultant Internal Medicine and Critical Care

Web:- Web:- http://www.medicinedoctorinchandigarh.com

Mob:- +91-7508677495Mob:- +91-7508677495

References:References:1.1. Brenner’s & Rector’s The Kidney 7Brenner’s & Rector’s The Kidney 7thth Ed. Ed.

2.2. Harrison’s Internal Medicine 16Harrison’s Internal Medicine 16thth Ed. Ed.

3.3. Oxford Textbook Of Clinical NephrologyOxford Textbook Of Clinical Nephrology

4.4. Manual of nephrology 5Manual of nephrology 5thth Ed. Ed.

5.5. Internet.Internet.

URINE EXAMINATIONURINE EXAMINATION

COMPOSITION OF URINECOMPOSITION OF URINE

Urine composition is affected mainly Urine composition is affected mainly by 3 factorsby 3 factors

Nutritional status Nutritional status State of metabolic processesState of metabolic processes Ability of the kidney to selectively Ability of the kidney to selectively

handle the material presented to it.handle the material presented to it.

URINE EXAMINATIONURINE EXAMINATION

URINE EXAMINATIONURINE EXAMINATION

GlomerulusGlomerulus proteinprotein

Proximal Proximal tubuletubule

GlucoseGlucose

Loop of Loop of henlehenle

Specific Specific gravitygravity

OsmolalityOsmolality

Collecting Collecting tubuletubule

pHpH

Physicochemical characteristics of urinePhysicochemical characteristics of urine pH 4.8 -8.0 (mean 6.1)pH 4.8 -8.0 (mean 6.1) Osmolality 38 – 1400 mOsm/Kg water(Avg =500-Osmolality 38 – 1400 mOsm/Kg water(Avg =500-

800)800) Specific gravity 1.003-1.030Specific gravity 1.003-1.030 Volume 600-2500(Avg 1200ml)Volume 600-2500(Avg 1200ml) Organic comtituents per 24 HoursOrganic comtituents per 24 Hours

Nitrogenous – total 25 - 35 gm Nitrogenous – total 25 - 35 gm Urea 15-30 gmUrea 15-30 gm Creatinine 1 -1.6 gmCreatinine 1 -1.6 gm Creatine 10-Creatine 10-

50mg(children,Excreated in Urine . 50mg(children,Excreated in Urine . in adults in hepatic or muscle in adults in hepatic or muscle disorders)disorders)

Ammonia 0.7(0.3-1) gmAmmonia 0.7(0.3-1) gm Uric acid 0.45 – (0.3 – 0.6) gmUric acid 0.45 – (0.3 – 0.6) gm Protein < 150 mgProtein < 150 mg Amylase 4-400 U/LAmylase 4-400 U/L

Inorganic Constituents per 24 Hours Inorganic Constituents per 24 Hours Sodium 4 gm on usual diet Sodium 4 gm on usual diet Phosphate 0.8-1.3 gm on usual diet Phosphate 0.8-1.3 gm on usual diet Chlorides 6(4-10) gm on usual dietChlorides 6(4-10) gm on usual diet Sulphur 2 gm Sulphur 2 gm Calcium < 150 mgCalcium < 150 mg

Cells And Casts Cells And Casts RBC 0-2 /high power field RBC 0-2 /high power field WBC 0-2 /high power field WBC 0-2 /high power field Bladder Cells -veBladder Cells -ve Squamous Cells -veSquamous Cells -ve Tubular cells -veTubular cells -ve Hyaline cast 0-5 /low power field Hyaline cast 0-5 /low power field Granular ,waxy,Granular ,waxy, Broad casts -veBroad casts -ve

Method of urine collectionMethod of urine collection

For microscopic analysis fresh mid – For microscopic analysis fresh mid – stream collection of second urine of stream collection of second urine of the morning under aseptic condition the morning under aseptic condition is required.is required.

Strenuous activity must be avoided Strenuous activity must be avoided several hours before collection. several hours before collection.

Sample should ideally be analysed Sample should ideally be analysed within 1 hr of voiding.within 1 hr of voiding.

Physical FeaturesPhysical Features

- -

ColourColour

1.1. Normal Normal pale -dark yellowpale -dark yellow

1.1. ColourlessColourless

2.2. Pink-Black Pink-Black

3.3. RedRed

4.4. Dark yellow-brownDark yellow-brown

Dilution ,Diabetes mellitus Dilution ,Diabetes mellitus /insipidus,diuretic or alcohol intake /insipidus,diuretic or alcohol intake

Haematuria Haematuria

Haemoglobinuria,Myoglobinuria, Haemoglobinuria,Myoglobinuria, Haematuria, Haematuria, Phenolphthalein,rifampicinPhenolphthalein,rifampicin

Jaundice.NitrofurantoinJaundice.Nitrofurantoin

1.1. Fresh urine darken up on Fresh urine darken up on standingstanding

Porphyria(dark brown), Porphyria(dark brown), Alkaptonuria(Black)Alkaptonuria(Black)

1.1. Brown-blackBrown-black

2.2. Green-blue green Green-blue green

3.3. Dark orangeDark orange

4.4. Dark blueDark blue

LevodopaLevodopa

Amtryptyline.phenol poisoning Amtryptyline.phenol poisoning

ClofazamineClofazamine

Hairdye poisoningHairdye poisoning

Physical FeaturesPhysical Features

ODOURODOUR

FruityFruity KetonesKetones

PungentPungent UTIUTI

MousyMousy Phenyl ketonuriaPhenyl ketonuria

Maple syrupMaple syrup Maple syrup urineMaple syrup urine

(sotolone)(sotolone)

Sweaty feetSweaty feet Isovaleric acidaemiaIsovaleric acidaemia

Rotten fish odourRotten fish odour Fish odour Fish odour syndromesyndrome

Launch Internet Explorer Browser.lnk

Physical FeaturesPhysical Features

TURBIDITYTURBIDITY

NORMALNORMAL CLEAR/CLEAR/TRANSPARENTTRANSPARENT

CloudyCloudy High concentration of High concentration of Bacteria,Leucocyte,EBacteria,Leucocyte,Erythrocytes,epithelial rythrocytes,epithelial cellscells

Milky/Cheese like Milky/Cheese like ChyluriaChyluria

Fresh urine gets Fresh urine gets cloudy on standingcloudy on standing

ppt of phosphates & ppt of phosphates & uratesurates

Physical FeaturesPhysical Features Relative densityRelative density Specific gravity Most commonly usedSpecific gravity Most commonly used

RefractometerRefractometer

Osmolality Most accurate assessment Osmolality Most accurate assessment

Dry chemistryDry chemistry

Specific gravitySpecific gravity

A function of no & wt of the dissolved solute particles.A function of no & wt of the dissolved solute particles.

Measured by URINOMETER (scale 1.000 to 1.060)Measured by URINOMETER (scale 1.000 to 1.060)

Needs correction factor for TEMP(+/- 0.001 for each Needs correction factor for TEMP(+/- 0.001 for each 3◦C 3◦C

above/below standard temp of above/below standard temp of instrument.instrument.

Proteins ↑ sp gt by 0.001 for each 0.4 g/dlProteins ↑ sp gt by 0.001 for each 0.4 g/dl

Glucose ↑ sp gt by 0.001 for each 0.27 g/dlGlucose ↑ sp gt by 0.001 for each 0.27 g/dl

Physical FeaturesPhysical Features In the absence of proteinuria or glucosuria if In the absence of proteinuria or glucosuria if

sp gt is > 1.040, +ce of abnormal substance sp gt is > 1.040, +ce of abnormal substance must be consideredmust be considered..

HighHigh Excessive sweating, Glycosuria, Excessive sweating, Glycosuria,

Albuminuria,Albuminuria,

All causes of oliguriaAll causes of oliguria

Acute nephritisAcute nephritis

Low(< 1.010)Low(< 1.010) Excessive water intakeExcessive water intake

Diabetes inspidusDiabetes inspidus

Chronic nephritisChronic nephritis

All causes of polyuria except diabetes All causes of polyuria except diabetes mellitus.mellitus.

Low & fixed(1.010 Low & fixed(1.010 to 1.012)to 1.012)

End stage renal diseaseEnd stage renal disease

ADH deficiencyADH deficiency

Arteriosclerotic kidneyArteriosclerotic kidney

Chemical FeaturesChemical Features

pHpH Normally range from Normally range from

4.5 to 8.0(Avg 6.1)4.5 to 8.0(Avg 6.1) Method:Method: 1.Dipstick Most 1.Dipstick Most

commonly used commonly used Utilizes methyl Utilizes methyl

red& bromothymol red& bromothymol as indicator as indicator covering pH 5 to 9covering pH 5 to 9

2.Digital electronic 2.Digital electronic pH meter pH meter

Acidic urineAcidic urine Alkaline Alkaline urineurine

Ketosis Diabetes, Ketosis Diabetes,

StarvationStarvation

Systemic acidosis Systemic acidosis Except with Except with

impaired renal impaired renal tubular functiontubular function, , Respiratory or Respiratory or

metabolic acidosismetabolic acidosis

UTI E. coli UTI E. coli

Acidification Acidification therapytherapy

Post prandial Post prandial alkaline tidealkaline tide

Systemic AlkalosisSystemic Alkalosis

Renal tubular Renal tubular acidosisacidosis

UTI Proteus/ UTI Proteus/ Pseudomonas Pseudomonas

infectioninfection

Alkalinization Alkalinization therapytherapy

Chemical FeaturesChemical Features HaemoglobinHaemoglobin

MethodMethod : : Dipstick Dipstick – Haemoglobin reacts with cumene peroxidase & – Haemoglobin reacts with cumene peroxidase & a orthotolidine(chromogen) to produce a blue colour.a orthotolidine(chromogen) to produce a blue colour.

Presence of Hb is expressed asPresence of Hb is expressed as Spots in +ce of intact RBCSpots in +ce of intact RBC Homogenous pattern in +ce of free Hb.Homogenous pattern in +ce of free Hb.

Measure up to as low as 0.1 – 0.6 mg/lMeasure up to as low as 0.1 – 0.6 mg/l

Myoglobin & Hb distinguised byMyoglobin & Hb distinguised by 5 ml urine + 2.8 g Ammonium sulfate, followed by 5 ml urine + 2.8 g Ammonium sulfate, followed by

centrifugation, HB ppts centrifugation, HB ppts while myoglobin does not.while myoglobin does not.

Spectrophotometry,Electrophoresis,Ultracentrifugation Spectrophotometry,Electrophoresis,Ultracentrifugation

False +ve False -ve

Ascorbic acid, high nitrite concAscorbic acid, high nitrite conc Myoglobin, large no:of bacteriaMyoglobin, large no:of bacteria

Chemical FeaturesChemical Features

Causes of Causes of HaemoglobinuriaHaemoglobinuria

IntracorpuscularIntracorpuscular ExtracorpuscularExtracorpuscular

1. Abnormalities of RBC 1. Abnormalities of RBC interiorinterior

a.a. Enzyme defectEnzyme defect

b.b. HaemoglobinopathiesHaemoglobinopathies

2. RBC membrane 2. RBC membrane abnormalitiesabnormalities

a.a. Hereditary Hereditary spherocytosisspherocytosis

b.b. Paroxysmal nocturnal Paroxysmal nocturnal haemoglobinuriahaemoglobinuria

c.c. Spur cell anemiaSpur cell anemia

Extrinsic factorExtrinsic factor

a.a. Antibody:immune Antibody:immune hemolysishemolysis

b.b. Microangiopathic Microangiopathic hemolysishemolysis

c.c. Infections, toxins.Infections, toxins.

Chemical FeaturesChemical Features PROTEINPROTEIN Urinary protein excreation does not exceed 150 mg/d for adults & Urinary protein excreation does not exceed 150 mg/d for adults &

140 mg/m2 of body surface.140 mg/m2 of body surface.

Causes Of Proteinuria As Related To QuantityCauses Of Proteinuria As Related To Quantity

DAILY DAILY PROTEIN PROTEIN EXCRETIONEXCRETION

0.15 to2.0g 2.0 to 3.5g >3.5 g

CAUSECAUSE Mild Glomerulopathies Tubular Proteinuria Overflow Proteinuria

Usually Glomerular

Always Glomerular

70 mg/d

5mg/d

10 mg/d 15 mg/d15 mg/d

35 mg/d

Tamm Horsfall Protein Blood Group Related AntigensAlbumin MucopolysaccaridesHormones and Enzymes Immunoglobulins

Composition Of Urinary ProteinComposition Of Urinary Protein

DetectionDetection Two methods.Two methods. 1.1. Dipsticks Dipsticks: : Dipstick analysis is used in most patients in out door setting.Dipstick analysis is used in most patients in out door setting. Paper strips are impregnated with bromocresol green & salicylate buffer when dipped in urine Paper strips are impregnated with bromocresol green & salicylate buffer when dipped in urine

undergo sequential colour changes from pale green to green & blue.undergo sequential colour changes from pale green to green & blue.

Binding of a protein is pH dependent.Binding of a protein is pH dependent.

Albumin binds at pH 5 – 7, other proteins at lower pH but with a lower affinity, while Albumin binds at pH 5 – 7, other proteins at lower pH but with a lower affinity, while Bence jones protein does not bind at any pH.Bence jones protein does not bind at any pH.

The resuts are graded asThe resuts are graded as Negative ( <10 mg /dl ) 2+ ( 100 mg /dl )Negative ( <10 mg /dl ) 2+ ( 100 mg /dl ) Trace ( 10 to 20mg/dl ) 3+ ( 300 mg/dl )Trace ( 10 to 20mg/dl ) 3+ ( 300 mg/dl ) 1+ ( 30mg /dl ) 4+ ( >1000mg/dl )1+ ( 30mg /dl ) 4+ ( >1000mg/dl )

Detect exclusively albumin.Detect exclusively albumin.

Sensitivity being for conc as low as 250 mg/lSensitivity being for conc as low as 250 mg/l

Microalbuminuria, globulin, bence jones protein or tubular proteins are not detected. Microalbuminuria, globulin, bence jones protein or tubular proteins are not detected.

2. 2. Precipitation methodsPrecipitation methods : Evaluate turbid occuring after proteis are ppt by : Evaluate turbid occuring after proteis are ppt by sulfosalicylic acid, trichloracetic acid,heat or acetic- sodium acetate buffer. sulfosalicylic acid, trichloracetic acid,heat or acetic- sodium acetate buffer.

QUANTITATIVE EVALUVATION

Method DescriptionDetection limit(mg/l)

Comments

Patients with persistent proteinuria should undergo 24-hr urine protein estimation. Patients with persistent proteinuria should undergo 24-hr urine protein estimation. The urinary creatinine concentration should be included in 24-hr measurement to The urinary creatinine concentration should be included in 24-hr measurement to determine adequacy of specimen (normal excretion in men=16 to 26mg/kg/day and in determine adequacy of specimen (normal excretion in men=16 to 26mg/kg/day and in women =12 to24 mg/kg/day as it depend on muscle mass)women =12 to24 mg/kg/day as it depend on muscle mass)

Biuret

Copper reagent, measures peptide bonds

50

Requires precipitation of proteins, used for 24-h measurement in some laboratories

Turbidimetric

Addition of trichloracetic or sulfosalicylic acids alters colloid properties and produces turbidity to be read in densitometer. Benzethomecin also used

50–100

Imprecise, different readings for albumin and globulin

Dye-binding

Indicator changes color in presence of protein (e.g. Coomassie brilliant blue) 50–100

Different proteins bind differently; several different dyes in use; used in many laboratories for 24-h excretion

Nephelometric

Specific antialbumin antibody used

Measures albumin excretion not total protein. Does not detect globulins

Quantifying ProteinuriaQuantifying Proteinuria

Spot Urinary Protein To Creatinine Spot Urinary Protein To Creatinine Ratio (Upr/Cr)Ratio (Upr/Cr)

It is an alternative to 24-hr urine protein It is an alternative to 24-hr urine protein estimationestimation

Recent studies indicates that it is more Recent studies indicates that it is more accurate than 24-hr urine protein accurate than 24-hr urine protein estimationestimation

The ratio is about the same numerically as The ratio is about the same numerically as number of grams of protein excreted per number of grams of protein excreted per dayday

QUALITATIVE EVALUATIONQUALITATIVE EVALUATION MethodsMethods Electrophoresis Electrophoresis Immunofixation Electrophoresis Immunofixation Electrophoresis Measurement of different proteinsMeasurement of different proteins

Microalbuminuria: defined as Microalbuminuria: defined as presence of albumin in urine above presence of albumin in urine above normal range of <30 mg/day but normal range of <30 mg/day but below detectable range with below detectable range with conventional dipstick methodology conventional dipstick methodology i.e.30-299 mg/day.i.e.30-299 mg/day.

Methods : Radioimmunoassay, enzyme Methods : Radioimmunoassay, enzyme immunoassay,nephelometric, & immunoassay,nephelometric, & turbidimetric.turbidimetric.

CausesCausesDiabetic mellitusDiabetic mellitus

High BPHigh BP

HypertriglyceridaeHypertriglyceridaemiamia

OCPOCP

HRTHRT

Causes Of ProteinuriaCauses Of Proteinuria

Primary Primary glomerulonephropatglomerulonephropat

hyhy

Secondary Secondary glomerulonephropatglomerulonephropat

hyhy

GlomerulonephropatGlomerulonephropathy associated with hy associated with

drugsdrugsMinimal change Minimal change disease disease

Idiopathic Idiopathic membranous membranous glomerulonephritis glomerulonephritis

Focal segmental Focal segmental glomerulonephritis glomerulonephritis

MembranoproliferatiMembranoproliferative ve glomerulonephritis glomerulonephritis

IgA nephropathyIgA nephropathy

Diabetes mellitus Diabetes mellitus

Collagen vascular Collagen vascular disorders (e.g., lupus disorders (e.g., lupus nephritis) nephritis)

Amyloidosis Amyloidosis

Infection (e.g., HIV, Infection (e.g., HIV, hepatitis B and C, hepatitis B and C, poststreptococcal poststreptococcal illness, malaria and illness, malaria and endocarditis) endocarditis)

Lymphoma, chronic Lymphoma, chronic renal transplant renal transplant rejectionrejection

Heroin Heroin

NSAIDs NSAIDs

Penicillamine Penicillamine

Lithium Lithium

Heavy MetalHeavy Metal

Causes Of ProteinuriaCauses Of Proteinuria

TubularTubular OverflowOverflow

Hypertensive Hypertensive nephrosclerosisnephrosclerosis

Tubulointerstitial disease due Tubulointerstitial disease due to to

Uric acid nephropathyUric acid nephropathy

Acute hypersenstivity Acute hypersenstivity

Interstitial nephritisInterstitial nephritis

Fanconi syndromeFanconi syndrome

Heavy metals & DrugsHeavy metals & Drugs

Sickle cell diseaseSickle cell disease

HemoglobinuriaHemoglobinuria

MyoglobinuriaMyoglobinuria

Multiple myelomaMultiple myeloma

AmyloidosisAmyloidosis

Approach to the pt with ProtenuriaApproach to the pt with Protenuria

Chemical FeaturesChemical Features GLUCOSEGLUCOSE Method:Method: 1. Dipsticks: 1. Dipsticks: Glucose oxidase Glucose oxidase

+ Glucose + Glucose Gluconic acid + H2O2 Gluconic acid + H2O2 H2O2 + orthotoludine H2O2 + orthotoludine

coloured productcoloured product

Highly specific & is sensitive to conc Highly specific & is sensitive to conc of 1-20 g/l.of 1-20 g/l.

2. Benidict’s Qualitative & 2. Benidict’s Qualitative & Quantitative test.Quantitative test.

False +veFalse +ve False-veFalse-ve

Ascorbic acid, Ascorbic acid, UTIUTI

Oxidising Oxidising substance substance

(hypochlorite)(hypochlorite)

Glycosuria with Glycosuria with hyperglycemiahyperglycemia

Glycosuria with Glycosuria with out out

hyperglycemiahyperglycemia

ENDOCRINEENDOCRINE : : Diabetis Diabetis mellitus, mellitus, AcromegalyAcromegaly. . PancreaticPancreatic : : Carcinoma, Carcinoma, severe severe PancreatitisPancreatitis,,

CNS dysfuctionCNS dysfuction ; ; Tumours or Tumours or haemorrhage in haemorrhage in hypothalamushypothalamus

DrugsDrugs : : steroids steroids thiazidesthiazides

Renal tubular Renal tubular dysfuctiondysfuction

PregnancyPregnancy

Chemical FeaturesChemical Features KETONE BODIESKETONE BODIES

Nornal value –veNornal value –ve

3 ketone bodies that can be 3 ketone bodies that can be detected are : detected are :

1. Acetone (2%)1. Acetone (2%) 2. Acetoacetic acid (20%)2. Acetoacetic acid (20%) 3. 3. ββ- Hydroxybutyric acid(78%)- Hydroxybutyric acid(78%)

Tests : 1. Dipsticks: contain Tests : 1. Dipsticks: contain sodium nitroprusside, amino acid sodium nitroprusside, amino acid & disodium phosphate.+ve test & disodium phosphate.+ve test indicated by purple colour.indicated by purple colour.

2. Rothera’s test2. Rothera’s test

3. Legal’test3. Legal’test

4. Diacetic acid test.4. Diacetic acid test.

DiabeticDiabetic Non Non DiabeticDiabetic

Diabetes Diabetes ketoacidosisketoacidosis

In infant & In infant & childchild

Acute febrile Acute febrile statesstates

Toxic states Toxic states with with

vomiting & vomiting & diarrhoeadiarrhoea

Hyperemesis Hyperemesis grvidarum grvidarum StarvationStarvation

Chemical FeaturesChemical Features BILE PIGMENTSBILE PIGMENTS

Normal values <0.02 mg%Normal values <0.02 mg%

MethodsMethods1.1. Foam testFoam test2.2. Iodine testIodine test3.3. Harrison testHarrison test4.4. Diazo testDiazo test

CAUSESOF HYPERBILIRUBINURIACAUSESOF HYPERBILIRUBINURIA

1.1. Moderate to severe hepatocellular damageModerate to severe hepatocellular damage2.2. Obstruction of bile ducyts, extra/ intrahepaticObstruction of bile ducyts, extra/ intrahepatic

Chemical FeaturesChemical Features Rare testsRare tests Leucocyte esterase : Leucocyte esterase : Based on esterase activity of Based on esterase activity of

granulocytesgranulocytes

Method is very specific for lysed leucocytes. Thus, in urine with Method is very specific for lysed leucocytes. Thus, in urine with alkaline pH / low sp gt , dipsticks, for esterase may be +ve, alkaline pH / low sp gt , dipsticks, for esterase may be +ve, while microscopic examination for leucocyte may be –ve. while microscopic examination for leucocyte may be –ve.

Nitrites Nitrites : presence of bacteria may be revealed by reduction : presence of bacteria may be revealed by reduction of nitrates to nitrites, shown by dipsticks containing an aromatic of nitrates to nitrites, shown by dipsticks containing an aromatic amine that reacts with nitrites to form a coloured diazonium amine that reacts with nitrites to form a coloured diazonium compound.compound.

Has low sensitivity & a high specificity.Has low sensitivity & a high specificity.

False –ve occur in alkaline urine, or in low / absent nitrate False –ve occur in alkaline urine, or in low / absent nitrate reducers like Pseudomonas, Stap. Albus.reducers like Pseudomonas, Stap. Albus.

Microscopic examinationMicroscopic examination The formed elementsThe formed elements Cells : ErythrocytesCells : Erythrocytes HematuriaHematuria : : defined as 2 -5 cells / high power field.defined as 2 -5 cells / high power field.

Persistent/Significant hematuria : > 3 RBC’s/HPF on 3 urialyses/ Persistent/Significant hematuria : > 3 RBC’s/HPF on 3 urialyses/ a single urinalysis with >100 RBC’s/ gross hematuria.a single urinalysis with >100 RBC’s/ gross hematuria.

Hematuria is defined as ‘non glomerular’ when 80% of RBC’s Hematuria is defined as ‘non glomerular’ when 80% of RBC’s show regular(orshow regular(or isomorphic) appearance.isomorphic) appearance.

And Glomerular when a similar proportioon of RBC’s are changed And Glomerular when a similar proportioon of RBC’s are changed (or dysmorphic) or atleast 5% of RBC’s are acanthocytes.(or dysmorphic) or atleast 5% of RBC’s are acanthocytes.

RBC morphology is an imp tool in the Mg of pt’s with isolated RBC morphology is an imp tool in the Mg of pt’s with isolated microscopic hematuria of unknown origin.microscopic hematuria of unknown origin.

Appearance of RBC in urine may reflect the appearance they Appearance of RBC in urine may reflect the appearance they have in the blood.have in the blood.

Microscopic examinationMicroscopic examination (a) Isomorphic (a) Isomorphic

erythrocytes (dark erythrocytes (dark cells have lost their cells have lost their haemoglobin haemoglobin content).content).

(b) Different types (b) Different types of dysmorphic of dysmorphic erythrocytes.erythrocytes.

(c) Different types (c) Different types of acanthocytes or of acanthocytes or G1 cells.G1 cells.

(d) Neutrophils (d) Neutrophils with their lobulated with their lobulated nucleus and nucleus and granular cytoplasmgranular cytoplasm

Microscopic examinationMicroscopic examination

Microscopic examinationMicroscopic examination The formed elementsThe formed elements Cells :Cells :

Leucocytes Leucocytes

NeutrophilsNeutrophils Most frequently found leucocytes in the urineMost frequently found leucocytes in the urine

Urinary tract infectionsUrinary tract infections

Active proliferative glomerulonephritis, acute or Active proliferative glomerulonephritis, acute or chronic interstitial nephritis, and urological chronic interstitial nephritis, and urological disorders. disorders.

LymphocytesLymphocytes Gradual or abrupt appearance of lymphocyturia Gradual or abrupt appearance of lymphocyturia in renal graft recipients is an early and sensitive in renal graft recipients is an early and sensitive marker of acute cellular rejection marker of acute cellular rejection

EosinophilsEosinophils Marker of acute interstitial nephritis, urinary Marker of acute interstitial nephritis, urinary tract infection, prostatitis, urinary tract infection, prostatitis, urinary schistosomiasis schistosomiasis

Microscopic examinationMicroscopic examination

The formed elementsThe formed elements CellsCellsRenal tubular Renal tubular cells cells

round to ovoid mononucleated cellsround to ovoid mononucleated cells

acute tubular necrosis (occur in clumps ) acute acute tubular necrosis (occur in clumps ) acute interstitial nephritis, acute cellular allograft interstitial nephritis, acute cellular allograft rejection and acute nephritic or nephrotic rejection and acute nephritic or nephrotic syndrome. syndrome.

Urothelial cellsUrothelial cells multilayered epithelium lining the urinary multilayered epithelium lining the urinary excretory tract Cells of the deep layers, when excretory tract Cells of the deep layers, when greater than or equal to 1/high-power field, are greater than or equal to 1/high-power field, are typical of conditions such as urolithiasis, bladder typical of conditions such as urolithiasis, bladder cancer, hydronephrosis, or are associated with cancer, hydronephrosis, or are associated with the presence of ureteric stents or prolonged the presence of ureteric stents or prolonged bladder catheterization .bladder catheterization .

In contrast, the superficial cells are a frequent In contrast, the superficial cells are a frequent finding in urinary tract infection finding in urinary tract infection

Squamous cells Squamous cells indicate a contamination of urine from vaginal indicate a contamination of urine from vaginal discharge discharge

Microscopic examinationMicroscopic examination (a) Different types of (a) Different types of

tubular cells.tubular cells.

(b) Urothelial cells from (b) Urothelial cells from the deep cell layers of the deep cell layers of the urothelium.the urothelium.

(c) An aggregate of (c) An aggregate of urothelial cells from the urothelial cells from the superficial cell layers of superficial cell layers of the urothelium.the urothelium.

(d) Squamous cells (d) Squamous cells surrounded by bacteria surrounded by bacteria (rods)(rods)

Microscopic examinationMicroscopic examination Lipids Lipids Present in urine mainly as Present in urine mainly as

droplets either free—isolated droplets either free—isolated or in aggregates or within or in aggregates or within casts and cells. In the latter casts and cells. In the latter case, they can form the so-case, they can form the so-called 'oval fat bodies', which called 'oval fat bodies', which are tubular cells or are tubular cells or macrophages gorged with macrophages gorged with lipids.lipids.

Typical finding in the urine Typical finding in the urine of patients with nephrotic of patients with nephrotic syndrome or heavy protein. syndrome or heavy protein.

Occasionally found in Occasionally found in polycystic kidney disease or polycystic kidney disease or with non-glomerular with non-glomerular diseases, Fabry's disease diseases, Fabry's disease

Microscopic examinationMicroscopic examination CastsCasts Elongated elements with a basic cylindrical shape that has some possible variation Elongated elements with a basic cylindrical shape that has some possible variation

due to bending, wrinkling, and irregular edges.due to bending, wrinkling, and irregular edges. They form within the distal tubules and the collecting ducts from the aggregation They form within the distal tubules and the collecting ducts from the aggregation

and transformation into a gel of the fibrils of Tamm–Horsfall glycoproteinand transformation into a gel of the fibrils of Tamm–Horsfall glycoprotein

CastCast Main clinical associationsMain clinical associations

Hyaline Hyaline

Hyaline–granularHyaline–granular

Granular Granular

Normal subject ,CHF, Diabetic nephropathy.Normal subject ,CHF, Diabetic nephropathy.

Normal subject ,Glomerulonephritis, PyelonephritisNormal subject ,Glomerulonephritis, Pyelonephritis

Glomerulonephritis, Pyelonephritis, Nephrotic syndrome Glomerulonephritis, Pyelonephritis, Nephrotic syndrome

Waxy Waxy

Fatty Fatty Renal insufficiency either acute or chronic Renal insufficiency either acute or chronic

Nephrotic syndrome Nephrotic syndrome

Erythrocyte/Erythrocyte/haemoglobinhaemoglobin

Glomerular bleeding,Proliferative/necrotizing Glomerular bleeding,Proliferative/necrotizing glomerulonephritisglomerulonephritis

Leucocyte Leucocyte Acute pyelonephritis, Acute interstitial nephritis, Proliferative Acute pyelonephritis, Acute interstitial nephritis, Proliferative glomerulonephritisglomerulonephritis

EpithelialEpithelial

Acute tubular necrosis, Acute interstitial Acute tubular necrosis, Acute interstitial nephritis ,Glomerulonephritisnephritis ,Glomerulonephritis

MyoglobinMyoglobin Acute renal failure associated with rhabdomyolysisAcute renal failure associated with rhabdomyolysis

Microscopic examinationMicroscopic examination (a) A hyaline cast with a (a) A hyaline cast with a

'fluffy' 'fluffy' appearance due to the appearance due to the

fibrillaryfibrillary substructure of Tamm–substructure of Tamm–

Horsfall Horsfall glycoprotein glycoprotein (b) A hyaline–granular cast. (b) A hyaline–granular cast. (c) A finely granular cast. (c) A finely granular cast. (d) A waxy cast(d) A waxy cast

(a) An erythrocyte cast.(a) An erythrocyte cast. (b) A leucocyte cast containing (b) A leucocyte cast containing packed neutrophils.packed neutrophils. (c) An epithelial cast. (c) An epithelial cast. (d) A fatty cast made of packed(d) A fatty cast made of packed lipid droplets lipid droplets

Microscopic examinationMicroscopic examination Crystals Crystals

Uric acid Uric acid precipitate at a pH less than or equal to 5.4. appear mostly as precipitate at a pH less than or equal to 5.4. appear mostly as lozenges lozenges

Calcium oxalate Calcium oxalate Two main types of calcium oxalate crystals: the mono- and the Two main types of calcium oxalate crystals: the mono- and the bihydratedbihydrated

Mainly found in acidic pH. Monohydrated calcium oxalate Mainly found in acidic pH. Monohydrated calcium oxalate crystals are birefringent, while the bihydrated are not. crystals are birefringent, while the bihydrated are not.

Calcium phosphate Calcium phosphate In alkaline urine In alkaline urine

prisms, needles, and star-like aggregates or as plates with a prisms, needles, and star-like aggregates or as plates with a granular surface. While the crystals polarize light, the plates do granular surface. While the crystals polarize light, the plates do not. not.

Triple phosphate Triple phosphate Precipitate at a pH greater than or equal to 7.0. Have a 'coffin Precipitate at a pH greater than or equal to 7.0. Have a 'coffin lid' appearance lid' appearance

Amorphous urates Amorphous urates and phosphates and phosphates

Appear as granular material, often in clumps, Appear as granular material, often in clumps,

urates are found in acid urine and are birefringent, while urates are found in acid urine and are birefringent, while phosphates precipitate only in alkaline urine and do not polarize phosphates precipitate only in alkaline urine and do not polarize light. light.

Cystine Cystine Thin, hexagonal, birefringent plates with irregular sidesThin, hexagonal, birefringent plates with irregular sides

marker of cystinuria, Found mostly in acid urine. marker of cystinuria, Found mostly in acid urine.

Crystals due to Crystals due to drugs drugs

sulfonamide sulfadiazine, acyclovir and indinavir ,triamterene, sulfonamide sulfadiazine, acyclovir and indinavir ,triamterene, coronary primidone, vitamin C ,amoxycillincoronary primidone, vitamin C ,amoxycillin

Microscopic examinationMicroscopic examination (a) Uric acid crystals (a) Uric acid crystals (b). Monohydrated (biconvex disc)(b). Monohydrated (biconvex disc) and bihydrated(bipyramidal) and bihydrated(bipyramidal) calcium oxalate crystals.calcium oxalate crystals. (c) A star-like calcium phosphate(c) A star-like calcium phosphate crystal Typical triple phosphatecrystal Typical triple phosphate crystalscrystals

(a) Aggregated cystine (a) Aggregated cystine crystals. crystals.

(b) 2,8-(b) 2,8-Dihydroxyadenine Dihydroxyadenine

crystalscrystals (c) Amoxycillin (c) Amoxycillin

trihydrate trihydrate crystals. crystals. (d) Amoxycillin (d) Amoxycillin

trihydrate trihydrate crystalscrystals

Microscopic examinationMicroscopic examination Clinical significance of crystalsClinical significance of crystals

Finding of few crystals of uric acid, calcium oxalate, and Finding of few crystals of uric acid, calcium oxalate, and calcium phosphate is usually irrelevant calcium phosphate is usually irrelevant

Crystalluria may be associated with intratubular Crystalluria may be associated with intratubular precipitation of crystals and acute renal failure(mainly in precipitation of crystals and acute renal failure(mainly in acute uric acid nephropathy, ethylene glycol poisoning, acute uric acid nephropathy, ethylene glycol poisoning, and after the administration of high dosages of drugs such and after the administration of high dosages of drugs such as sulfadiazine, acyclovir, indinavir, naftidrofuryl oxalate, as sulfadiazine, acyclovir, indinavir, naftidrofuryl oxalate, vitamin C, amoxycillin)vitamin C, amoxycillin)

To monitor the patients with recurrent metabolic To monitor the patients with recurrent metabolic urolithiasis urolithiasis

Some crystals are always pathologic cystine which is a Some crystals are always pathologic cystine which is a marker of cystinuria marker of cystinuria

MICROORGANISMMICROORGANISM Bacteria : FBacteria : Frequently seen in urine sediments, either as rods or cocci requently seen in urine sediments, either as rods or cocci

presence of leucocytes increases the probability of a real infection .presence of leucocytes increases the probability of a real infection .

Fungi Fungi

Candida is the most frequent yeast .Candida is the most frequent yeast . Most frequent cause of candida in the urine is contamination , can also Most frequent cause of candida in the urine is contamination , can also

grow in the urinary tract, mostly in patients with diabetes mellitus, grow in the urinary tract, mostly in patients with diabetes mellitus, structural abnormalities, indwelling catheters, prolonged antibiotic structural abnormalities, indwelling catheters, prolonged antibiotic treatment or immunosuppression. treatment or immunosuppression.

Protozoa :Protozoa :

Trichomonas vaginalisTrichomonas vaginalis -round or pear shaped , -round or pear shaped , has four flagella, found in the urine of both sexes, mostly as a consequence has four flagella, found in the urine of both sexes, mostly as a consequence

of genital contamination .of genital contamination .

Parasites :Parasites :

Schistosoma haematobiumSchistosoma haematobium : adult form lives and lays the eggs in the : adult form lives and lays the eggs in the vesical plexus and veins draining the ureters, is endemic in several vesical plexus and veins draining the ureters, is endemic in several geographic areas such as Nile valley, West Africa, Arabia, etc. Responsible geographic areas such as Nile valley, West Africa, Arabia, etc. Responsible for haematuria, chronic renal failure due to obstructive uropathy or bladder for haematuria, chronic renal failure due to obstructive uropathy or bladder cancer cancer

MICROORGANISMMICROORGANISM (a) A 'dirty' urine (a) A 'dirty' urine

background showing background showing many bacteria (rods) many bacteria (rods) and debris.and debris.

(b) Candida (b) Candida albicans. albicans.

(c) Trichomonas (c) Trichomonas vaginalis (arrows) vaginalis (arrows) (note the flagella).(note the flagella).

(d) Two eggs of (d) Two eggs of Schistosoma Schistosoma haematobium haematobium

Diagnostic Evaluation Diagnostic Evaluation When proteinuria is found on a dipstick analysis, the urinary When proteinuria is found on a dipstick analysis, the urinary

sediment should be examined microscopically for-sediment should be examined microscopically for-

Fatty casts, free fat or oval fat bodies

Nephrotic range proteinuria (>3.5 g /24 hours)

Leukocytes, leukocyte casts with bacteria

Urinary tract infection

Leukocytes, leukocyte casts without bacteria

Renal interstitial disease

Normal-shaped erythrocytes Suggestive of lower urinary tract lesion

Dysmorphic erythrocytes Suggestive of upper urinary tract lesion

Erythrocyte casts Glomerular disease

Waxy, granular or cellular casts Advanced chronic renal disease

Eosinophiluria Drug-induced acute interstitial nephritis

Hyaline casts No renal disease; present with dehydration

The interpretation of main urine sediment findingsThe interpretation of main urine sediment findings NephrotiNephrotic c sediment sediment

characterized by large amounts of lipids characterized by large amounts of lipids and variable amounts of hyaline, and variable amounts of hyaline, granular, or epithelial casts. granular, or epithelial casts.

Erythrocytes are absent or only a few, Erythrocytes are absent or only a few, (10/high-power field). (10/high-power field).

Neutrophils are also absent Neutrophils are also absent

Minimal-change Minimal-change disease,disease,

Focal segmental Focal segmental glomerulosclerosis, glomerulosclerosis,

Membranous Membranous nephropathy, nephropathy,

Diabetic nephropathy,Diabetic nephropathy,

Amyloidosis, Amyloidosis,

urinary differences may urinary differences may existexist

Microscopic haematuria is Microscopic haematuria is absent in about 50 %of absent in about 50 %of patients with minimal-patients with minimal-change disease, while it is change disease, while it is almost always present in almost always present in membranous nephropathy membranous nephropathy

lipiduria is more marked lipiduria is more marked and frequent in and frequent in membranous nephropathy membranous nephropathy than in minimal-change than in minimal-change diseasedisease

Nephritic Nephritic sediment sediment

Distinguishing feature Distinguishing feature

+ce of abundant erythrocyturia +ce of abundant erythrocyturia associated with RBC /haemoglobin casts.associated with RBC /haemoglobin casts.

Neutrophils are also frequent in low Neutrophils are also frequent in low numbers (usually ≤10hpf). numbers (usually ≤10hpf).

Leucocyte casts are possible, but they Leucocyte casts are possible, but they are rare. are rare.

Other findings are: tubular cells, hyaline, Other findings are: tubular cells, hyaline, granular, epithelial, and waxy casts. granular, epithelial, and waxy casts.

Active proliferative Active proliferative glomerulonephritis glomerulonephritis

>/=100 RBC/ hpf is >/=100 RBC/ hpf is almost invariably almost invariably associated with associated with Extracapillary/necrotiziExtracapillary/necrotizing glomerulonephritisng glomerulonephritis

Monitoring the urinary Monitoring the urinary sediment in patients with sediment in patients with proliferative proliferative glomerulonephritides is glomerulonephritides is important because the important because the sediment reflects to some sediment reflects to some extent the progressive extent the progressive changes in the kidneys changes in the kidneys

The interpretation of main urine sediment findingsThe interpretation of main urine sediment findingsNephrotic and Nephrotic and nephritic nephritic sediment sediment

Co-existence of lipiduria with abundant Co-existence of lipiduria with abundant erythrocyturia and cylindruria which erythrocyturia and cylindruria which also encompasses erythrocyte/ also encompasses erythrocyte/ haemoglobin casts. haemoglobin casts.

Mesangiocapillary Mesangiocapillary glomerulonephritis,glomerulonephritis,

Lupus nephritis with both Lupus nephritis with both proliferative and proliferative and membranous changes,membranous changes,

Henoch–Schönlein Henoch–Schönlein purpura, purpura,

Sediment of Sediment of acute tubular acute tubular necrosisnecrosis

Characterized by variable amounts of Characterized by variable amounts of tubular cells, which often appear tubular cells, which often appear damaged damaged

Epithelial and granular casts are Epithelial and granular casts are another typical finding. another typical finding.

Additional elements Additional elements depends on the cause of depends on the cause of acute tubular necrosis.acute tubular necrosis.

Due to rhabdomyolysis, Due to rhabdomyolysis, myoglobin casts may be myoglobin casts may be seen,seen,

while RBC may be present while RBC may be present in acute interstitial in acute interstitial nephritis,nephritis,

Crystals in crystalluric Crystals in crystalluric forms of acute tubular forms of acute tubular necrosis (hyperoxaluria or necrosis (hyperoxaluria or drugs )drugs )

Sediment of Sediment of urinary tract urinary tract infectioninfection

Association of bacteriuria with Association of bacteriuria with leucocyturia leucocyturia

false negative due to the false negative due to the lysis of leucocytes at lysis of leucocytes at alkaline pH, alkaline pH,

false-positive caused by false-positive caused by leucocyturia and leucocyturia and bacteriuria secondary to bacteriuria secondary to urine contamination from urine contamination from genitalia. genitalia.

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