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Compendium UrinalysisUrinalysis with Test Strips

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CHEMSTRIP, COBAS, COBAS U, COMBUR-TEST,DIABUR-TEST, KETO-DIABUR-TEST, LIFE NEEDSANSWERS, MICRAL, MICRAL-TEST, MIDITRON,REFLOTRON, URISYS, URISYS 1100, URISYS 1800and URISYS 2400 are trademarks of Roche.

TESTSIMPLETS is a trademark of Diagonal GmbH& Co. KG

©2008 Roche

Roche Diagnostics GmbHD-68298 MannheimGermanywww.roche.com

Authors: Dr. Ewald F. Hohenberger

Dr. Horst Kimling

1Urine Examination with Test StripsHistory of urinalysis with test strips 3Indications for urine test strips 7Pre-analytical treatment and test performance 11

Characteristics of Urine Test Strips from Roche 19

Specific gravity 23

pH 25

Leukocytes 27

Nitrite 29

Protein (Albumin) 33

Glucose 37

Ketones 41

Urobilinogen 43

Bilirubin 47

Blood (erythrocytes/hemoglobin) 49

Microscopical and Bacteriological ExaminationThe test strip sieve 55Microscopic assessment of the sediment 57Urine culture 60Urine cytology with Testsimplets 63

Automated Urinalysis 64

Detection of Microalbuminuria with Micral-Test 77

AppendixThe kidneys and the efferent urinary tract 81Cell atlas – urine sediment/urine cytology 86Glossary of specialist medical terms 95Further reading 107

Contents

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History of urinalysis with test strips

In many cultures urine was once regardedas a mystical fluid, and in some cultures itis still regarded as such to this day. Itsuses have included wound healing, stim-ulation of the body’s defences, and exam-inations for diagnosing the presence ofdiseases.

Modern medicine has at its disposal avariety of quick and hygienic test methodspermitting safe and reliable analysis ofurine test specimens. The starting pointfor diagnosing a wide range of patholo-gical conditions is, however, simple visualexamination of the urine, and a long pathhad to be travelled to the development ofthe modern test strips now used routinelyfor determining the urine status. Let usnow take a quick look at this long devel-opment process.

It all started over 2000 years agoThe origin of visual urine diagnostics, theoldest method of examining body fluids,can be traced back to ancient Egypt,where polyuria and haematuria are men-tioned as states of disease in old medicalpapyri. Hippocrates (ca. 400 BC) observedcertain changes in the odour and color ofurine in the presence of fever, and point-ed out the importance of examining thepatient’s urine. The Indian physician Cara-ka (ca. 100 AD) described ten pathologi-cal kinds of urine, including urines thatcontained sugar and bacteria.

No medical teaching of the past was,however, so important, and none had

such lasting influence, as that of ClaudiusGalenus of Pergamum, also known asGalen, who in the second century ADcombined the medicine of his day, dividedinto a number of groups, into one majorsystem with his doctrine of humoralpathology: “It is not solid organs that arethe seat of disease but the four body flu-ids or humours: blood, phlegm, black bile,and choler or yellow bile. Disease is dueto an imbalance of these fluids, and thenature and site of the disease can beestablished from the composition and

Fig. 1: Uroscopy in the 15th century

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appearance of the humours. An illnesstherefore also shows itself in the urine.”This doctrine dominated medical thinkingup to the 16th century. In pathology theteaching of Galen of Pergamum was infact abandoned only in the 19th century.

In the 10th century the Arab physicianIsaac Judaeus, basing himself on Galen’shumoralism, developed a scheme of hu-mours with which he raised the urinefindings to the level of an almost infalliblediagnostic criterion for all states of dis-ease. The extreme consequence of thistheory was so-called uromancy or uros-copy practiced in the Middle Ages (Fig. 1),which according to modern views wasdevoid of any scientific basis. Over 20shades of color were distinguished in the

urine (from crystal clear via camel hairwhite, blackberry red, and pale green toblack), and corresponding conclusionswere drawn about the patient’s illness (Fig. 2). The development went so far thatall that was wrong with the human bodywas believed to be reflected as in a mirrorin the urine specimen. This view served asa basis for the “urine fortune-telling,”which was so caustically criticized byhumanistic physicians in the 16th century.

In the 16th century Paracelsus promptedexamination of the urine by the methodsof alchemy, but the thinking of his time,tinged by ideas of magic and astrology,prevented his proposals from developinginto forerunners of medical and chemicalanalysis of the urine.

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Fig. 2: A urine glass disc with 20 color nuances (1491 AD)


pathological urine constituents. Criticismswere voiced at the time that doctors activein general practice had to do too muchchemistry, since the tests were all basedon wet chemistry. The first “test strips”were developed by the Parisian chemistJules Maumené (1818–1898) when, in1850, he impregnated a strip of merinowool with “tin protochloride” (stannouschloride). On application of a drop ofurine and heating over a candle the stripimmediately turned black if the urinecontained sugar. Despite its simplicity thetest was not widely accepted, and it tookanother 70 years or so before the Vien-nese chemist Fritz Feigl (1891–1971) pub-lished his technique of “spot analysis.”

In the intervening years prominent physi-cians, above all in Britain, concernedthemselves with the development of theforerunners of modern test strips. Thus,English physiologist George Oliver(1841–1915) marketed his “Urinary TestPapers” in 1883. The principle in this casewas to fix the reagents required for thepreparation of solutions in high concen-trations on filter paper or cloth, to facili-tate the work of the practitioner.

Reagent papers were already commer-cially obtainable at the beginning of thiscentury from the chemical company ofHelfenberg AG. A test for the presence ofblood by a wet-chemical method usingbenzidine became known in 1904, and itwas not long before an analogous benzi-dine paper test appeared on the market.

From uromancy to the idea of clinicalchemistry of the urineIt was only towards the end of the 18thcentury that doctors interested in chemis-try turned their attention to a scientificbasis of urinalysis and to its use in practi-cal medicine. Writing in 1797, the physi-cian Carl Friedrich Gärtner (1772–1850)expressed a wish for an easy way of test-ing urine for disease at the patient’s bed-side.

In the same year a work appeared in Bri-tain in which the chemist William Cruik-shank (1745–1800) described for the firsttime the property of coagulation on heat-ing, exhibited by many urines. This obser-vation led English physician Richard Brightto speak of the “albuminous nature of uri-ne” and to describe this clinical symptom of nephritis in 1827 in “Reports of MedicalCases.” This marked the breakthrough ofqualitative urine chemistry into medicine.

In the decades that followed a number ofchemical urinalyses were introduced intoclinical general practice, such as exami-nations of the urine for protein, sugar, andacetone. However, these examinationswere associated with considerable timeand effort, and the results were not veryspecific, e.g. the reduction methods ofFehling or Nylander for the detection ofsugar in urine.

With the arrival of chemical urine diag-nostics the year 1840 marked a true boomfor methods aimed at the detection of

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Triumph of the test stripsAll these “dry reagents” still did not de-serve the designation of “dry chemistry” inthe modern sense of the term, but theymust be regarded as rudimentary fore-runners of the modern test systems. Evenif the basic principle of reagent drying fora time did not undergo any change, urinediagnostics made major progress in the1930s. The informative power and the reli-ability in particular were distinctlyimproved, and test performance itselfbecame progressively easier.

Urine test strips in the sense used todaywere first made on industrial scale andoffered commercially in the 1950s. Thecompany Boehringer Mannheim, today atop leader on the world market under thename of Roche, launched its first Comburtest strips in 1964. Even though the teststrips have changed their externalappearance little since the 1960s, theynow contain a number of revolutionaryinnovations. New impregnation tech-niques, more stable color indicators, andthe steady improvement in color gradationhave all contributed to the fact that theuse of urine test strips has now becomeestablished in clinical and general prac-tice as a reliable diagnostic instrument.

The parameter menu offered has steadilygrown longer in the intervening decades.Today Combur-Test product line fromRoche can be used for the recognition ofthe early symptoms of the following three

major disease categories:� diseases of the kidneys and the uro-

genital tract� metabolic diseases (diabetes mellitus)� liver diseases and haemolytic disor-

ders

Diabetic and hypertension-determinednephropathies have been diagnosed earlywith the aid of Micral-Test in the presenceof microalbuminuria.

Indications for urine test strips

� the result is obtained quickly� the test is easy and inexpensive� high sensitivity (diagnostic sensitivity)� sufficiently high diagnostic specificity

A field study carried out in seven Euro-pean countries with over 11,000 urinesamples illustrates the value of screeningwith urine test strips (Fig. 3). A pathologi-cal urine finding (after checking for nitrite,protein, glucose, ketones, urobilinogen,and blood) was diagnosed in 16% of “nor-mal healthy persons,” in 40% of out-patients, and in 57% of hospitalized pa-tients.

With the aid of routine examinations earlysymptoms of the following three groupsare identified:� diseases of the kidneys and the uri-

nary tract� carbohydrate metabolism disorders

(diabetes mellitus)� liver diseases and haemolytic disor-

ders

Diseases of the kidneys and urogenital tractScreening parameters:� leukocytes� nitrite� protein� blood� specific gravity� pH

Urine test strips are a central diagnosticinstrument, their ease of use yieldingquick and reliable information on patho-logical changes in the urine. Their signi-ficance lies primarily in first-line diag-nostics. Routine testing of the urine withmultiparameter strips, allowing a deter-mination of the complete urine status, istherefore the first step in the diagnosis ofa very wide range of disease pictures.

Indications for urine test strips:� screening within the framework of

routine examinations� treatment monitoring� self-monitoring by patients� general preventive medicine

Screening within the framework of routine examinationsWithin the framework of routine examina-tions urine test strips are used for screen-ing both in hospitals and in general prac-tice. The aim of screening is early identifi-cation of likely patients by examination oflarge groups of the population. No directdiagnoses are established on the basis ofthe screening results, which serve only asa basis for further microscopic, bacterio-logical, or clinicochemical examinations ofthe urine.

Urine test strips can satisfy all therequirements for effective screening:

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Diseases of the kidneys and the urogeni-tal tract often remain asymptomatic for along time. Renal function disturbancesfrequently lie dormant for many years,leading eventually to often irreversiblesevere late damage. Kidney failure as theterminal stage of various primary and sec-ondary nephropathics (Fig. 4) can only betreated by renal substitution therapy suchas dialysis or kidney transplantation.Effects are also possible on other organsystems, especially on the cardiovascularsystem. The cardinal symptom of a urinarytract infection is the detection of signifi-cant bacteriuria (nitrite positive) andleukocyturia (leukocytes positive) bymeans of test strips.

The following non-specific symptomsoccur time and time again in patients withurinary tract infections or pyelonephritisand require further clarification to avoidpossible late consequences such as urae-mia, hypertension, and cardiovascularcomplications:� tiredness and exhaustion� chronic headaches� persistent lack of appetite� loss of weight� nausea and vomiting� intermittent rises in temperature and

fever of unclear origin (in childrensome 50% of urinary tract infectionsare manifested by fever)

� pale yellow skin color, puffy appearance

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Importance of urinalysis as a screening procedure

“normal”persons 16%

outpatients40%

hospitalizedpatients 57%

Frequency of pathological urine in different groups of people.Parameters: nitrite, protein, glucose, ketones, urobilinogen, blood

A field study carried out in seven European countries with over 11,000 urine samples

Fig. 3: Frequency of pathological urines


� in patients with congenital urological disorders approx. 57%

� in gout patients approx. 65%� in patients after catheterization,

instrumentation, and operations on the urinary tract

Regular checking for urinary tract in-fections and infectious kidney diseases,especially in women and elevated-riskpatients, enables treatment to be startedearly as a result of diagnosis in an earlystate of the disease, with good prognosisof the otherwise serious conditions. Afterthe end of the therapy further controlchecks are also necessary to catch anyrelapses in good time.

The following characteristic symptoms aremuch more rare:� proteinuria� “weak bladder,” a “bladder cold”� burning and pain during micturition� polyuria, dysuria, pollakiuria� bed-wetting in older children� pains in the lumbar and kidney region.

In certain risk groups the danger of uri-nary tract infections and pyelonephritis isparticularly high:� in pregnant women 4–8%� in hypertensive subjects approx. 14%� in older people 8–18%� in diabetics up to 20%� in patients with urinary

calculi approx. 50%

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Type II diabetes2,9%

Cystic/polycystickidney diseases7,5%

Analgesics nephropathy2,9%

Glomerulonephritis25,6%

Pyelonephritis/interstitial nephritis18%

Type I diabetes7,4%

Hypertension10,2%

Others10,9%

Unclearorigin14,6%

Source: Demography of Dialysis and Transplantation in Europe, 1993

Fig. 4: Causes of dialysis and kidney transplants


Carbohydrate metabolism disorders (inter alia diabetes mellitus)Screening parameters:� glucose� ketones

Around 30–40% of type I diabetics andaround 20% of type II diabetics suffer intime from a nephropathy, and early recog-nition of diabetes is therefore of major significance for the further state of healthof these patients.

Liver diseases and haemolytic disordersScreening parameters:� urobilinogen� bilirubin

In many liver diseases the patients oftenshow signs of pathology only at a latestage. Early diagnosis allows appropriatetherapeutic measures to be instituted ingood time, avoiding consequential dam-age and further infections.

Treatment monitoringTreatment monitoring with the aid of urinetest strips allows the treating doctor tocheck on the results of the prescribedtherapy, and if necessary to introduce anychanges into the therapeutic strategy. Anadditional benefit of such monitoring isimproved patient compliance.

Monitoring is particularly useful in twoclinical conditions:In diabetes mellitus combined checks forglucose and ketones are advisable for thepurpose of early detection of any dieteticerrors by changes in the metabolic statusand for their correction.

Patients suffering from hypertension runan increased risk of developing kidneydamage in the course of their condition.Micral-Test allows early detection of inci-pient nephropathy.

Self-monitoring by patientsUnder their doctor’s instructions patientscan benefit directly from the advantagesof urine test strips. This applies particular-ly to diabetics, where the idea of self-monitoring of the metabolic status (de-terminations of glucose and ketones) isself-evident.

General preventive medicineSpontaneous preventive monitoring athome has meanwhile become widespreadin the population. For example, a check onthe first morning urine for an asymp-tomatic urinary tract infection can becarried out without any problems on aday-to-day basis. The same applies to anexamination of the urine 2 hours after acarbohydrate-rich main meal to check forthe presence of diabetes mellitus. Thewhole family is often involved in suchpreventive monitoring.

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Pre-analytical treatment and test performance

Depending on the time and nature of theurine specimen collection, a distinction isdrawn between:� spontaneous urine� first morning urine (after a night’s

rest)� second morning urine (collected

before noon)� timed urine (usually 24-hour urine)� midstream urine� bladder puncture urine

The first morning urine has proved itsworth for most test purposes. As a rule itensures sufficiently long residence ofurine in the bladder, and its compositionis independent of the daily variations due

Reliable analytical results can only beobtained from a urine specimen that hasbeen collected, transported and storedproperly. To this day the diagnostic possi-bilities of urinalysis are often not utilizedto the full because correct pre-analyticaltreatment cannot be ensured.

Sample collectionThe urine collection and dispatch equip-ment should always comprise clean andsterile disposable containers, made as arule from plastic. Important patient data(surname, first name, date of birth, sender,collection date and time) should beaffixed to the container in a waterproofmanner before the sample collection.

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Fig. 5: Collecting a mid-stream urine sample

Wash hands. Take lid off specimen container

and place with inside surface

facing upwards.

First void a small amount of urine into the toilet,

then fill the specimen container half full,

void remaining urine into the toilet.

Replace the lid on the specimencontainer beingcareful not to

touch the inside;give the container

to the nurse or laboratory.

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to food and fluid intake and physicalactivity. For checks on glucosuria it is bestto use urine passed about 2 hours after acarbohydrate-rich meal.

Contamination is frequent in normal“spontaneous” urine collected withoutany special hygienic precautions, espe-cially in the case of women, and consistsof leukocytes in the presence of dischargeand of erythrocytes in the presence ofmenstruation. For this reason no urinediagnostics should be attempted inwomen during and 2–3 days after men-struation.

Correct sample collection is made easierby leaflets with a detailed description ofthe procedure for patients and medicalpersonnel.

Sample storageExamination of the urine with test stripsshould be carried out at the latest 2 hoursafter micturition, since longer standingtimes can lead to false results owing tothe following influences:

� disintegration (lysis) of leukocytes anderythrocytes

� proliferation of bacteria� bacterial degradation of glucose� a rise in pH due to ammonia formed

as a result of bacterial degradation ofurea

� oxidation of bilirubin and urobilinogen,especially in sunlight

These changes in the specimen can beslowed down if the urine is kept in asealed container in a refrigerator.

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Parameter Stability in urine Influencing Interference Remarksmeasured 4–8 °C 20-25 °C factors factors

Specific Fluid intake, pH > 7 Precipitation changesgravity diuretics the specific gravity

pH Unstable Unstable Diet (meat ↓, Rise on formationvegetarian ↑) of ammonia

Leukocytes 1–4 h 1–4 h Vaginal secretion Strong color of Fast lysis aturine ↑ specific gravity < 1.010 High glucose and and pH > 7.protein values ↓ Mix urine specimenCertain wellantibiotics ↑ or ↓

Nitrite 8 h 4 h Bacterial count Strong color of Antibiotics inhibiturine ↑ nitrite formationAscorbic acid ↓Phenazopyridine ↑

Protein 7 days 1 day Physical activity Ejaculate ↑(albumin) pregnancy Preservatives ↑

Glucose 8 h 2 h Pregnancy, Bacteria ↓fever, old age

Ketones 6 h 2 h Starvation, Phenylketones ↑ Test is more sensitivefasting, Phthaleins ↑ to acetoacetic acidfever SH compounds ↑ than to acetone

Urobilinogen 2 h Light ↓ Oxidation in airStrong color of urine ↑Phenazopyridine ↑

Bilirubin 2 h Light ↓ Oxidation in airAscorbic acid ↓Phenazopyridine ↑

Blood 1–4 h 1–4 h Menstruation, Oxidizing cleaning Fast lysis at (erythrocytes) strong physical agents ↑ specific gravity < 1.010

activity and pH > 7.Mix urine specimenwell

Tab. 1: Storage conditions, influencing factors and interference factors

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Parameter Stability in urine Influencing Interference Remarksmeasured 4–8 °C 20-25 °C factors factors

In sediment:Bacteria 24 h Urinary pH Cells are lysed inCasts 1–4 h Unstable dependence on pH andEpithelial cells hours osmolality.Erythrocytes 1–4 h 1–4 h Osmolality < 300 mmol/LLeukocytes 1–4 h 1–4 h reduces storage stability

Urine culture Low pH, Results too low orantibiotics, false-negative resultsinfections outsidethe bladder(kidney stones,prostate), fastidiousmicroorganisms

Indwelling catheter, Results too high orcollection technique false-positive results(children, oldpersons),delayedworking-up

Tab. 1 (Continued): Storage conditions, influencing factors and interference factors


listed in the table below.White turbidity can be due to:� phosphates precipitating in alkaline

urine (test: the precipitate redissolveson acidification with acetic acid)

� pyuria in massive bacterial or fungalinfections (microbial count >107/mL)

� lipiduria in the presence of a nephrot-ic syndrome or on contamination withointments

� massive proteinuria

Odour of the urineStriking odour changes of clinical signifi-cance include:� odour of fresh fruit or of acetone in

the presence of ketonuria (sign ofpossible presence of metabolic aci-dosis, most often due to fasting oruncontrolled diabetes mellitus)

� “fetor hepaticus,” a musty odour ofurine and breath in the presence ofhepatic encephalopathies

� odour of alcohol in the presence ofintoxication due to ethanol

� odour of ammonia in urinary tractinfections due to urea-splitting bac-teria; odour of hydrogen sulfide in uri-nary tract infections with proteinuriadue to putrefacient bacteria

� a wide range of various odours due tointoxications and after certain foods

PneumaturiaPneumaturia (presence of fine gas bub-bles) is a rare symptom pointing to thepresence of a fistula between the urinarytract and the intestine.

Macroscopic assessment of urinespecimensMacroscopic assessment of the urine (itscolor and odour) is of little diagnostic value, but within the framework of visualexamination of the specimens any strikingcolor changes are usually reported aswell.

The normal urine volume of an adult issome 700–2000 mL/day. An output ofmore than 2500 mL/day is classified aspolyuria, an output of less than 500mL/day as oliguria, and an output of lessthan 100 mL/day as anuria.

Color of the urineThe color of normal urine is due to thepresence of porphyrins, bilirubin, urobilin,uroerythrin, and some other, still unidenti-fied, compounds. Striking changes shouldbe reported in terms of definite colors:“red,” “brown,” “green,” etc.

Color changes are caused most often bydrugs and their metabolites. A brick-redsediment is usually due to precipitation ofurates in acidic urine (test: the precipitateredissolves on gentle warming). Haema-turia is recognized by the presence ofbrown-red turbidity with a red-brownsediment. Darkening can also occur in thepresence of substances other than those

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Points to avoid at all times� Residues of cleaning agents or

disinfectants falsify the results (false-positive findings for blood, protein andglucose)

� Freezing of the urine specimen willdestroy leukocytes and erythrocytesand hence make the specimen un-usable for subsequent microscopicexaminations

� Specimens must not be centrifugedprior to test strip analysis

� Specimens must not be exposed todirect sunlight

Quality assuranceQuality assurance in urinalysis includes inaddition to the analysis itself the opera-tions of sample collection, preservation,preparation and transport. It is thereforenecessarily interdisciplinary and requiresinvolvement of the patient.

Test performance1. Collect the urine specimen in a clean

sterile container (preferably a dispos-able container).

2. Dip the test strip in the urine for nolonger than 1 second.

3. On drawing the strip out of the samplerun its edge over the rim of the con-tainer to remove excess liquid.

4. After 60 seconds (60–120 seconds forleukocytes) compare the reaction colorin the test area against the color scaleon the label.

Colors occurring only on the edges orones that develop only after more than 2 minutes are not relevant for diagnosticpurposes.

Points to note� Urine examinations with test strips

should be carried out within 2 hoursat the latest

� The urine specimen should be mixedthoroughly prior to the test

� The specimens must always be kept ina refrigerator (at +4°C) if the testscannot be done within 2 hours of theurine collection

� At the time of testing the samplesmust be at room temperature

� The test strip tubes must be stopperedagain immediately after the removal ofa test strip

� Remember to label the urine container

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Characteristics of urine test strips from Roche

The absorbent paper layer takes upexcess urine and stops the test area col-ors from running.

Semiquantitative resultsIn the event of a pathological finding acolor change occurs in the respective testarea. The color intensity allows a semi-quantitative evaluation of the result.

Unequivocal color scaleSpecial colorfast printing colors on thevial label allow easy and reliable evalua-tion of the results.

Safe and hygienic handlingThe reagent paper and the underlyingabsorbent paper are covered over with athin porous nylon mesh and fixed to astable white carrier foil (Fig. 6).

The nylon mesh� protects the reagent pad from con-

tamination � fixes the reagent pad reliably to the

carrier foil� ensures uniform color development

through uniform penetration of theurine into the test area

� prevents falsification of the color by glue

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Carrier foil

Reagent paper

Absorbent paper

Nylon mesh

Fig. 6: Structure of test strips from Roche

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Long storage lifeA drying agent in the cap of the plastictube protects the sensitive test strips fromatmospheric humidity. The test strips arestable up to the expiry date specified onthe package when stored and usedaccording to the directions.

High sensitivityAn important evaluation criterion for the

quality of urine test strips is the practicaldetection limit (Fig. 7), i.e. the concen-tration of the substance determined atwhich the test gives a positive result in 90 out of 100 different samples. The low-er the detection limit, the more sensitivelycan pathological changes be identified bythe test strip in question.

The practical detection limit is made suchthat even slight pathological changes inthe urine are made visible by a clear colorchange in the test area.

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practicaldetection limit

concentrationof the analyte

100

90

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Fig. 7: Practical detection limit


In a study published in 1992 Brigden et al.1 showed that an oral dose of as little as100 mg vitamin C per day, or even a singleglass of fruit juice, may already produceascorbic acid concentrations of some 10 mg/dl in the urine. With conventionalurine test strips these concentrations maybe high enough to provoke interference.Combur-Test strips from Roche remainstable even in the presence of high con-centrations of vitamin C, and false-nega-tive reactions to blood and glucose arehardly ever observed.

Risks of ascorbic acid interferenceIt must be borne in mind that over 20% ofall urine specimens may contain sufficientascorbic acid concentrations to involve arisk of interference in testing for bloodand glucose. The risk of false-negativeresults increases particularly sharply inthe flu season, when people turn in largenumbers to vitamin supplements, affect-ing the diagnosis of the following clinicalpictures:� Blood: glomerulonephritis,

pyelonephritis, lithiasis, tumours

� Glucose: diabetes mellitus, glucosurias determined by kidney damage

Protection against interference due to vitamin CVitamin C (ascorbic acid) inhibits the oxi-dation reactions for blood and glucose inthe test area and can therefore lead tofalse-negative results in the presence ofhaematuria and glucosuria.

The test strips of the Combur-Test productline are protected against this interfer-ence by incorporation of iodate. Any vita-min C present in the urine sample is thuseliminated by oxidation. If the very wideuse of ascorbic acid in the food industry istaken into account, and the numbers ofpeople putting their faith in vitamin sup-plements, it obviously makes a decisivedifference in haematuria and glucosuriadiagnostics whether the urine test stripused is protected from vitamin C interfer-ence.

Significance of vitamin CVitamin C is added to many foods andbeverages on account of its outstandingantioxidant and preservation activity; forexample it is added to flour, bread, cakesand pastries, to sausages, cereal flakes,fruit and vegetable juices, to beer, andeven to champagne. Many people in addi-tion take pure vitamin C prophylacticallyin the form of vitamin tablets. All this canlead to elevated vitamin C levels in theurine and to interference in urinalysiswhen using test strips.

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Additional test areas for ascorbic acid onstrips not protected from vitamin C inter-ference will reveal an excessive vitamin Cconcentration in the patient’s urine, andthe urine examination must then berepeated at a later time. On account oftheir potential falsification, the results arenot used.

Reference1 High incidence of significant urinary ascorbic

acid concentrations in a West Coast popula-tion – implications for routine urinalysis. Mal-colm L. Brigden et al., Clin. Chem. 38/3,426 – 431 (1992).

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Specific gravity

gravity of urine is today only of subordi-nate importance. Besides, controlled con-ditions are a prerequisite, such as fluiddeprivation for 12 or 24 hours.

The diuresis factor can be used in theassessment of other urine parameters bymeans of the specific gravity; slightlyelevated analyte values, e.g. the levels ofprotein, are more meaningful in sampleshaving a low specific gravity than inconcentrated urine.

Specific gravity is also significant in ana-lysis of the urine for narcotics or for pro-scribed drugs in athletes, as it may pointto manipulation of the specimen.

Values below 1.010 g/mL are of analyticalsignificance, because in such urine ery-throcytes and leukocytes undergo rapidlysis. This may explain negative sedimentresults with a positive test strip reaction.

Test principleThe test determines the ion concentra-tions in urine by reaction with a complexformer and detection of the released pro-tons.

Non-ionic constituents of the urine suchas glucose or urea are not determined.

Sources of errorIn the presence of small amounts of pro-tein (100–500 mg/dL) there is a tendencyto read off high values. The same occursin the case of ketoacidotic urine.

An increase in urine specific gravity dueto glucose concentrations >1000 mg/dL (>56 mmol/L) is not determined by teststrips.

At pH 7 or higher the test result obtainedhas to be increased by 0.005 g/mL.

Influencing factorsThe specific gravity of urine dependsprimarily on the amount of fluids drunk bythe patient, but factors such as heavysweating, the effect of low temperatures,or increased urine output provoked bydiuretically active agents (e.g. coffee orcertain medicines) also exert an influence,so that even in healthy persons the valuescan vary from 1.000 to 1.040 g/mL.

Clinical significanceThe diagnosis of kidney function distur-bances (e.g. a reduced concentrationcapacity) by determining the specific

Specificgravity

pH

Sources of errorIf the specimen is allowed to stand for toolong, the urine may become alkaline (pH>7) as a result of bacterial decompositionof urea. The pH is then diagnosticallymeaningless.

Test principleThe pH test relies on a combination ofthree indicators, methyl red, bromthymolblue and phenolphthalein. In the pHrange of 5–9 this gives a color gradationgoing from orange to yellow-green and toblue.

Reference rangesCourse over the day: pH 4.8–7.4Morning urine: pH 5– 6

25

pHTest principle

Acidic urine: mixed color Orange Alcaline urine: mixed color green

OBrBr

yellow Bromthymol blue

OH –H

+HSO3

-

+

+

+

N(CH3)2

red Methyl red yellow

COOH COOH

= N N = NNH

N(CH3)2

–H

+H

OBrBr

blue

O

SO3

-

O

OHR R

-H2O+2 NaOH

Phenolphthalein

OOH

R

O

R

OO Na

O Na

-

-

+-

+

+

+

Fig. 8: Principle of the urine pH test

pH

pH

Influencing factors� Nutrition� Animal protein leads to acidic urine, a

vegetarian diet to strong alkalization� Metabolic status� Various diseases� Medicines

Clinical significancePersistently acidic or alkaline urine pointsto the possibility of a disturbance of theacid-base balance. Persistently alkalinepH values are evidence of an infection inthe urogenital tract. High pH values arealso of analytical significance becauseerythrocytes and leukocytes are lysedfaster in such urine, which can explain thecombination of negative sediment resultswith a positive test strip reaction.

Acidosis (pH <7) and alkalosis (pH >7)can also be due to the following causes:

Metabolic acidosis� diabetic acidosis� fasting� medicines and toxins� kidney failure� renal tubular acidosis (pH rarely below

6.0)

Respiratory acidosis� retention of CO2 (emphysema)

Metabolic alkalosis� severe potassium deficiency� excessive intake of alkalis� diuretics� vomiting

Respiratory alkalosis� infections� fever

26

Leukocytes

LeukocytesTest principle

OH + HOONH

SO2 SO2

R1

R2

Indoxyl

Indoxyl ester Indoxyl

Diazonium salt Dye (violet)

Esterase

NH

OH

NH

OH

NH

R1R2

NH

+ N N

ONH

O

N N

+ -

Fig. 9: Principle of the leukocyte test

Specificity� The test detects the esterase activity

of granulocytes and histiocytes (histi-ocytes are also produced in the pres-ence of inflammatory processes and inmicroscopic examinations they areusually not distinguished from leuko-cytes)

� Not only intact but also already lysedleukocytes are detected, which are notfound by urine sediment microscopy

� The test does not react to urine-path-ogenic bacteria and trichomonads

� Epithelia, spermatozoa, and erythro-cytes do not have any effect in theconcentrations in which they canoccur in urine

Test principleThe leukocytes excreted in the urine arealmost exclusively granulocytes, whoseesterase activity is detected in the teststrip reaction. The test zone contains anindoxyl ester, which is cleaved by thegranulocyte esterase. The free indoxylreleased reacts with a diazonium salt toform a violet dye.

Practical detection limit10–25 leukocytes/µL

Reference rangesNormal <10 leukocytes/µLBorderline 10–20 leukocytes/µLPathological >20 leukocytes/µL

27

Leuko-cytes

Leukocytes

� pH values in the range of 4.5–9, nitrite in the presence of urinary tractinfections, ascorbic acid, and ketonesdo not exert any influence

Sources of error� If the urine is strongly colored, this

intrinsic color could mask the colorformed by the strip reaction

� Protein excretion in excess of 500mg/dL and glucose excretion of over 2 g/dL could lead to a weaker color de-velopment, as could high doses of ce-phalexin and gentamicin

� Preservatives falsify the test result(false-positive reading in the case offormaldehyde, false-negative in case of boric acid). Medication with imipe-nem, meropenem and clavulanic acid)could lead to false-positive results.

Clinical significanceLeukocyturia is an important guide symp-tom of inflammatory diseases of the kid-neys and efferent urinary tract, e.g. � bacterial infections: cystitis, urethritis,

acute and chronic pyelonephritis� abacterial infections due to yeasts,

fungi and viruses� parasite infestations, e.g. schistosomi-

asis� glomerulopathies� analgesics nephropathies� intoxications� urine-voiding disturbances

Leukocyturia occurs substantially moreoften in women than in men. This is

explained on the one hand by the morefrequent occurrence of urinary tract in-fections in women and on the other by therisk of contamination of the urine spe-cimens by leukocytes from a vaginal dis-charge. One must therefore reckon with a positive leukocyte test in 30–40 % ofspontaneous urine specimens fromwomen.

The great majority of positive leuko-cyte findings is due to the presenceof a bacterial urinary tract infection.

If an inflammation is chronic or healed up, in particular, it is not rare to obtain apositive leukocyte reaction and yet fail tofind any bacteria in the urine. This condi-tion is known as “abacterial” leukocyturia.In chronic pyelonephritis leukocyturia isoften the only symptom in the intervalsbetween the acute episodes – the addi-tional symptoms associated with theacute course, such as fever, kidney pains,proteinuria and erythrocyturia, are absent.

Abacterial leukocyturia can in additionconstitute important evidence for thepresence of tuberculosis or tumours.

Clarification of leukocyturiaThe following procedure is recommendedfor further differential diagnostics:� clarification of proteinuria, haematuria,

nitrituria� determination of the microbial count� microscopic examination of the sedi-

ment for leukocyte casts

28

29

Test principle Nitrite is detected by the same principleas that of Griess’ test. Any nitrate presentin the urine is converted by bacterialreduction into nitrite:

Nitrate bacterial reduction in urine nitrite

The aromatic amine sulfanilamide reactswith nitrite in the presence of an acidbuffer to form a diazonium compound,which is coupled with 3-hydroxy-1,2,3,4-tetrahydrobenzo-(h)-quinoline to form anazo dye. The intensity of the red color is a measure of the nitrite concentrationpresent, but says nothing about the sever-ity of the infection.

Nitrite

Practical detection limit11 µmol/L (0.05 mg/dL).

Reference rangeBacteria-free urine does not contain anynitrite.

SpecificityThe nitrite detection is specific for thepresence of bacteriuria; the reaction isindependent of the pH.

A single negative test does not exclude a urinary tract infection, because themicrobial count and the nitrate content ofthe urine can vary. Absence of color onrepeated testing is also not reliable evi-dence for the absence of a urinary tract

+ -+

Nitrite

H2N–SO2

H2N–SO2 H2N–SO2

H2N – SO2

Diazonium salt Azo dye (red)Coupling component

Sulfanilamide Diazonium saltNitrite

Test principle

NH3 + NO2 N + 2 H2O

N=N OH

OHN + N

N

NH N

H

H

H +

+

+

Fig. 10: Principle of the nitrite test

Nitrite

Nitrite

infection, since a pathogenic microorgan-ism that does not form nitrite could bepresent. If there is clinical suspicion of aninfection, therefore, it is advisable to go onin all cases to a determination of themicrobial species and the microbial count.

Sources of errorFalse-negative results may occur as aresult of:� strong diuresis with frequent voiding

of urine (the incubation time of theurine in the bladder is too short)

� fasting states� parenteral nutrition� vegetable-free diet� specimens that have been left stand-

ing for too long (test done more than 4 hours after the specimen collection)

False-positive results may be due to:� bacterial contamination of urine left to

stand for too long� treatment with medicines containing

phenazopyridine

Clinical significancePresence of nitrite in the urine is one ofthe most important symptoms of a bacte-rial urinary tract infection. A positive teststrip result in the nitrite field is a reliablepointer to the presence of an acute infec-tion.

After respiratory tract infections, urinarytract infections are the most commonbacterial diseases. Their spread in thepopulation varies with age and sex,

increasing strongly with advancing age(Fig.11). Women are particularly affectedby this condition. During pregnancy, reg-ular checking for urinary tract infections isindispensable. Men suffer from theseinfections increasingly after the age of 60.Recognition and early treatment of urinarytract infections is of decisive importance,because a progressive infection may leadto chronic kidney failure, pyelonephriticatrophic kidneys, and uraemia.

Normal urine does not contain any nitrite.The ingestion of even large amounts ofnitrite or nitrite-containing therapy doesnot result in nitrite excretion. Any nitriteexcreted through the urinary tract cantherefore be attributed exclusively to bac-terial reduction of nitrate.

Normal nutrition as a rule ensures a suffi-ciently high content of nitrate in the urinefor the detection of bacteria. The most fre-quent pathogen responsible for urinarytract infections, E. coli, and most of theother urine-pathogenic organisms (Kleb-siella, Aerobacter, Citrobacter, Salmonella,and to some extent also enterococci,staphylococci, and Pseudomonas) reduceurinary nitrate to nitrite and can thereforebe detected indirectly with test strips.

30

Nitrite

� Normal vegetable-containing nutritionon the preceding day. A normalvegetable-containing diet generallyensures a urinary nitrate level sufficientfor performance of the test

� Exclusion of antibacterial therapy� In the presence of antibiotic treatment

or chemotherapy the enzyme meta-bolism and the microbial populationare suppressed, so that not enoughnitrite is formed for the test. All anti-bacterial therapy must therefore bediscontinued at least 3 days beforethe urinalysis

On average about 50% of urinary tractinfections can be identified by the nitritetest, but under the following conditionsthe recognition rate can be improved tomore than 90%:� Repeated checking of the first morn-

ing urine. Being a biological process,nitrite formation requires a reasonablylong residence time of the urine in thebladder, at least 4–6 hours

31

Fig. 11: Relative frequency of positive nitrite findings in urine samples

% of Positive Nitrite Findings

Age ≤ 20 21–30 31–40 41–50 51–60 > 60

Sex � � � � � � � � � � � �

Group

Normal subjects 2.4 0.6 3.3 0.9 3.7 0.7 5.9 1.7 1.8 0.4 9.8 2.2

Outpatients 8.8 4.4 3.4 4.1 4.7 6.2 8.2 5.9 9.8 9.9 16.7 8.5

Inpatients 10.8 12.9 11.7 10.4 17.3 13.0 17.1 17.2 16.0 13.5 20.6 18.6

Protein (Albumin)

Medicines such as quinine, quinidine,chloroquine, sulfonamides, and penicillinhave virtually no effect on the color re-action. The same applies to pH values of5–9 and to various urine specific gravity.

Practical detection limitA clear color reaction is obtained at aconcentration of 6 mg/dL albumin andabove, situated somewhere between thenegative color field and 30 mg/dL on thecomparison scale.

Evaluation30 mg/dL was selected as the first positivecomparison color, because pathologicalproteinurias are normally above this value.Color changes that do not unequivocallyreach the value of 30 mg/dL are normallyassessed as negative. In patients with

Test principleThe detection reaction relies on the so-called protein error of pH indicators.

The protein test area contains a buffermixture and an indicator which under-goes a color change from yellow to greenin the presence of protein, even thoughthe pH is held constant.

Reference rangeBelow 10 mg/dL (for total protein).

Specificity The indicator reacts particularly sensitive-ly to albumin excreted in the presence ofkidney damage. The sensitivity to otherproteins (e.g. γ-globulins, Bence-Jonesprotein, proteoses, peptones, mucopro-teins) is lower.

33

Protein

Yellow3',3",5',5"-tetrachlorphenol-3,4,5,6-tetrabromsulfophthalein(neutral form)

GreenAnion of this compound

Test principle

-H

ProteinSO3 SO3Br

BrBr

Br

Cl

OCl Cl

Cl

OH O

Br

BrBr

Br

Cl

OCl Cl

Cl

+-

-

-

Fig. 12: Principle of the test for protein

Protein(Albumin)

Protein (Albumin)

clinically manifest kidney damage, whooften have only low-grade proteinuria,this finding cannot, however, be used forcontrolling the course of their illness.

Sources of errorFalse-positive results are obtained underthe following conditions:� infusion of polyvinylpyrrolidone

(a blood substitute)� presence of residues of disinfectants

containing quaternary ammoniumgroups or chlorhexidine in the urinecontainer

� phenazopyridine medication

Clinical significanceProteinuria is a frequent symptom in renaldiseases, but it is also non-specific. It isnot proof of nephropathy, nor does its ab-sence exclude nephropathy. Detection ofprotein in the urine should thereforealways be followed by differential diag-nostics.

Benign proteinuriaIn persons with healthy kidneys protein-urias are observed predominantly up tothe age of 30, and account for up to 90%of the proteinurias observed in this agegroup. The causes of these benign pro-teinurias are in particular physical stress(sport), emotional stress, orthostatism andlordosis. Proteinurias associated with

34

Daily course of urinary protein excretion

Greatest physical activity

Protein in urine, mg/h3

2

1

0 000 400 800 1200 1600 2000 2400

mg/h

Fig. 13: Daily course of urinary protein excretion

Protein (Albumin)

Renal proteinuriaAn increase in the permeability of theglomerular capillaries due to pathologicalprocesses leads to the development ofrenal proteinuria.

Renally determined proteinurias are as arule persistent and are observed in bothnocturnal and daytime urine. In generalthe level is in excess of 25 mg/dL, themost pronounced proteinurias being ob-served in nephroses. In glomerulonephri-tis the protein excretion is usually 200–300mg/dL, but lower values must be reckonedwith in the event of glomerulonephritisassociated with few symptoms. This pro-teinuria is usually accompanied by micro-haematuria.

Tubular proteinuria can be due to lesionsof the tubule cells and/or to a disturbanceof the tubular uptake of proteins fromglomerular filtrate. This proteinuria isencountered e.g. in the presence of pyelo-nephritis, cystic kidneys, and gouty kid-neys.

Intermittent protein excretion is oftenfound in chronic pyelonephritis.

Postrenal proteinuriaPostrenal proteinuria can occur followinginflammation of the bladder or prostateand on bleeding in the urinary tract.

hypothermia, heat, pregnancy, or the useof vasoconstrictively acting drugs are alsoas a rule benign. Benign proteinuria hasbeen observed in 20% of women duringpregnancy.

Benign proteinurias occur intermittently.While in the morning urine the proteinexcretion is normal, values reaching 500 mg/dL may be observed in the courseof the day. On the basis of this propertybenign proteinuria is relatively easilydistinguished from the pathological formby repeated testing of the first morningurine (Fig. 13).

Additional examinations of the urine fornitrite, blood, and leukocytes, and mea-surement of the blood pressure, give nor-mal findings if the proteinuria is benign. Ifa benign proteinuria is diagnosed, how-ever, it should be monitored in order todetect the development of a kidney dis-ease in good time.

Extrarenal proteinuriaProtein is detected in the urine in manymostly acute clinical pictures, such as col-ics, epileptic fits, infarcts, strokes, headinjuries, and postoperative states. Theseproteinurias disappear after the extrarenalcause has been eliminated. Proteinuriasdue to fever are usually harmless, but theydo require clinical supervision and coursemonitoring.

35

Glucose

Practical detection limitFor ascorbic-acid-free urine the practicaldetection limit is around 2.2 mmol/L (40 mg/dL), so that even slightly patho-logical glucosurias can be detected withhigh reliability. The upper limit of physio-logical glucosuria in the first morning urine is around 0.8 mmol/L (15 mg/dL).

SpecificityThe enzymatically catalyzed reactionsequence ensures that glucose is the onlyurinary constituent that will react and givea positive test result.

Test principleThe detection of glucose is based on a specific glucose-oxidase-peroxidase re-action in which D-glucose is oxidizedenzymatically by atmospheric oxygen toδ-D-gluconolactone. The hydrogen per-oxide formed oxidizes the indicator TMBunder peroxidase catalysis, to give a blue-green dye which on the yellow test papercauses a color change to green.

Reference rangeFasting morning urine <1.1 mmol/L

(< 20 mg/dL)Daytime urine < 1.7 mmol/L

(< 30 mg/dL)

37

Glucose

OH

O OOH

OH

+ O2

CH2OH

3,3',5,5'-Tetramethylbenzidin

HO HOH O + H2O2

OH

CH2OH

HO

Test principle

H2O + dye (blue) POD

GOD

H2N NH2 + H2O2

β-D-Glucose Oxygen Hydrogenperoxide

Fig. 14: Principle of the glucose test

Glucose

Glucose

Ketones do not interfere, and the pH ofthe urine similarly does not exert anyinfluence on the test result. However, be-fore its analysis with test strips the urinemust not be acidified.

Sources of errorThe best known interference factor forenzymatic glucose detection in urine, thepresence of ascorbic acid (vitamin C), hasbeen largely eliminated in this test. Atglucose concentrations of 5.5 mmol/L(100 mg/dL) and higher even high ascor-bic acid contents practically never lead tofalse-negative test results.

Other metabolic products and drugmetabolites which have a reducing actionand can exert an influence on the reac-tion, such as the degradation products ofsalicylates, normally occur only in small amounts in the urine and cause inter-ference only in their sum.

False-positive results can occur as aresult of the presence of residues of per-oxide-containing or other strongly oxidiz-ing cleaning agents in the urine contain-er.

Clinical significanceThe determination of glucose in urine hasa high diagnostic value for early detection

38

Renal threshold for glucose

Renal threshold

Glucose concentrationin plasma

600

400

200

0 0 100 200 300 mg/100 mL

mg/min

Tubular resorption

Urinary glucose excretion

Glomerular filtration

Amount of glucose transported

Fig. 15: Renal threshold

Glucose

hold, which in diabetics is on averagehigher than in healthy persons. In olderpatients in particular the renal thresholdis often so high that no glucose appears inthe urine despite diabetic blood glucoselevels.

In spite of all these restrictions, detectionof urinary glucose is of major significancefor early detection, control, and self-mon-itoring of diabetes.

The following conditions are seen as riskfactors for diabetes mellitus:� obesity� hyperlipoproteinaemia� hyperuricaemia� gout� hypertension� coronary, cerebral, and peripheral

blood flow disorders� diseases of the liver and the bile tract� chronic urinary and respiratory tract

infections� chronic skin diseases

Further risk factors are:� Age over 40� Familial predisposition to diabetes� Mothers of children with a large

weight at birth (over 4.5 kg)

Renal glucosuriaIf the renal threshold is significantly lowe-red owing to reduced glucose reabsorp-tion in the renal tubules, increased glu-cose excretion will be found in the urineeven if the blood glucose is normal, below

of diabetes mellitus and for course controlor self-monitoring by patients. On the oth-er hand, absence of glucosuria does notexclude a disturbance of the glucosemetabolism, and in particular it does notexclude diabetes mellitus. Another pointto note is that glucosuria may also be dueto clinical conditions other than diabetes.

Glucosuria develops when the tubularreabsorption of glucose in the kidneys(the renal threshold) is exceeded (Fig. 15).The renal threshold is normally at a bloodglucose level of 150–180 mg/dL (8.3–10mmol/L), but it is often elevated in olderpeople and in persons who have had dia-betes mellitus for many years.

Diabetes mellitusEvery second to third diabetic has notbeen identified. The reason for this is thepaucity of symptoms at the beginning ofthe disease. Older diabetics in particulartend to view their complaints, such asquick fatigability, frequent passage ofurine, slow healing of wounds, and failingvisual acuity, as part of the “normal age-ing process” and never suspect that theunderlying cause might be a metabolicdisease. However, early diagnosis is ofdecisive importance, because early treat-ment can prevent or at least postpone thedelayed damage.

Most diabetics exhibit glucosuria. Thedegree of the glucose excretion dependson the severity of the metabolic distur-bance and on the individual renal thres-

39

Glucose

the diabetic range. The frequently obser-ved glucosuria in the course of pregnancy(in 5–10% of cases) is also due normallyto a lowering of the renal threshold. Afterthe woman has given birth this kind ofglucosuria is no longer observed.

Alimentary glucosuriaThis can occur after an extremely largeingestion of carbohydrates.

Glucosuria in the presence ofkidney damageSymptomatic renal glucosuria occurswhen kidney function falls to 30% or lessof normal renal performance. This renaldiabetes mellitus is also observed in acuterenal failure.

Diabur-Test 5000Keto-Diabur-Test 5000These two test strips have been designedespecially for monitoring the urinaryglucose level in diabetes mellitus. Themeasurement range of the glucose field,extended compared with the multiteststrips, permits an exact differentiation ofthe urine’s glucose content from 0 to 5%.

The glucose test in (Keto-)Diabur-Test5000 is also based on the glucose-oxi-dase-peroxidase reaction and is specificfor glucose. Other sugars, like fructose orgalactose, do not react.

40

Ketones

SpecificityGlucose, protein, and ascorbic acid do notinterfere.

Sources of errorPhenylketones and phthalein compoundsproduce red colors on the test patch.These are, however, quite different fromthe violet colors produced by ketone bo-dies. Captopril, mesna (2-Mercaptoethan-esulfonic acid sodium salt) and other sub-stances containing sulfhydryl groups mayproduce false-positive results.

Clinical significanceKetones (acetoacetic acid, β-hydroxy-butyric acid, and acetone) occur in theurine when an increased fat degradation

Test principleThe detection of ketones is based on theprinciple of Legal’s test. Acetoacetic acidand acetone react with sodium nitroprus-side and glycine in an alkaline medium togive a violet color complex. The reaction isspecific for these two ketones. β-hydro-xybutyric acid does not react.

Reference rangeBelow 0.5 mmol/L (below 5 mg/dL) foracetoacetic acid.

Practical detection limitThe test is substantially more sensitive foracetoacetic acid (detection limit 5 mg/dL= 0.5 mmol/L) than for acetone (detectionlimit about 40 mg/dL = 7 mmol/L).

41

Ketones

Na2 [Fe(CN)5NO] + CH3–C–R + NaOH Na3[Fe(CN)5N=CH–C–R] + H2O

Sodium nitroprusside Ketone

O

Color complex (violet)

Test principle

O

OH

Fig. 16: Principle of the ketone test

Ketones

Ketones

takes place in the organism owing toinsufficient supply of energy in the form ofcarbohydrates.

Predominance of lipolysis over lipogenesisleads to increased free fatty acid levels inserum, and on their breakdown in the liv-er more acetyl-coenzyme A is formed thancan be utilized by other metabolic pro-cesses, e.g. the tricarboxylic acid cycle.This excess is converted into acetoaceticacid, which in turn is partly transformedinto β-hydroxybutyric acid and to asmaller degree into acetone.

Ketonuria in diabetes mellitusDetection of ketones in the urine (aceto-acetic acid and acetone) is particularlyimportant in diabetes mellitus for check-ing metabolic decompensation.

Precomatose and comatose states in dia-betes are almost invariably accompaniedby ketoacidosis, with the exception ofhyperosmolar comas. Relative or absoluteinsulin deficiency causes reduced glucoseutilization in fat and muscle cells and trig-gers increased lipolysis. The resultingketones in combination with other patho-physiological changes of the dysregula-ted metabolism (dehydration, electrolyteshifts) can lead to diabetic coma.

Diabetic coma is a life-threatening event,and ketonuria is an early symptom of themetabolic dysequilibrium.

All diabetics should check their urine forketones on a regular basis. In juvenile andinsulin-dependent diabetics in particular,in whom coma may develop within a fewhours, a check for ketones in urine shouldtherefore always form part of self-moni-toring, side by side with the checks onurinary glucose.

Progressive ketoacidotic metabolic dys-regulation may occur if the diabeticpatient is not sufficiently well managedwith insulin. The condition is character-ized by ketone excretion in urine, anodour of acetone on the breath, andincreased urinary levels of glucose.

Ketonuria of non-diabetic originKetones are also found in the urine in thefollowing situations:� Fasting states� Slimming diets low in carbohydrates,

or protein-rich nutrition, or total star-vation diets. The acid-base turnover,however, remains fully compensated ifgood kidney function is ensured bysufficient intake of fluids. Checking forketones also serves in such cases as acontrol of compliance with the diet

� Acetonaemic vomiting in smallchildren

� Fever, especially in the presence ofinfectious diseases

� Pernicious vomiting in pregnancy� Congenital metabolic diseases

42

43

Urobilinogen

Complete absence of urobilinogen in theurine, perhaps on complete obstruction ofthe common bile duct, cannot be detect-ed.

SpecificityThe test is specific for urobilinogen anddoes not react with other diazo-positivesubstances. It is also not subject to theinterference known in the Ehrlich test. No red color is formed in the presence ofporphobilinogen, indican, p-aminosali-cylic acid, sulfonamides, sulfonylureas,and other substances occurring in theurine.

Test principlep-methoxybenzenediazonium fluorobo-rate, a stable diazonium salt, forms a redazo dye with urobilinogen in an acidmedium.

Reference rangeBelow 17 µmol/L (below 1 mg/dL).

Practical detection limitThe practical detection limit is around 7 µmol/L (0.4 mg/dL), at which level theurobilinogen also present in normal urinegives a pale pink color. Differentiationbetween normal and pathological urine ispossible by means of color comparison.

+ -

Urobilinogen

H3C–O Azo dye (red)

Diazonium salt

BF4 + UrobilinogenN N

Test principle

Acidmedium

Fig. 17: Principle of the urobilinogen test

Urobili-nogen

Urobilinogen

Sources of errorFalse-negative results occur under thefollowing conditions:� prolonged standing of the urine

specimen, especially in direct sunlight,leads to oxidation of urobilinogen

� formaldehyde preservation with concentrations in excess of 70 mmol/L(200 mg/dL) in the urine

False-positive results:� may be due to drugs that color the

urine red or that are red in an acidmedium (e.g. phenazopyridine)

A momentary yellow coloration of the testpaper points to the presence of largeamounts of bilirubin, but the reading isnot impaired. In rare cases a green or blue color may develop slowly about 60 seconds after immersion in the urine.

Clinical significanceUrobilinogen is formed by bacterialreduction from bilirubin secreted into theintestine with the bile. It is then reab-sorbed into the bloodstream and is sub-sequently broken down in the liver andpartly excreted in the urine.

Detection of urobilinogen in the urine isindicative of two possible causes:� a disturbance of liver function due to

a primary or secondary liver disease� an increased degradation of haemo-

globin due to a primarily haemolyticdisease or secondarily to other dis-ease pictures

Urobilinogen is excreted in increasedamounts in the urine when in the entero-hepatic circulation of the bile pigmentsthe functional capacity of the liver isimpaired or overloaded, or when the liveris bypassed.

Overloading of the functionalcapacity of the liverIf large amounts of bilirubin, and thereforealso of urobilinogen, are formed as aresult of increased degradation of haemo-globin, the functional capacity of the livermay be exceeded even though the livercan deal with 2–3 times the normalamounts of urobilinogen. The urobilino-gen not processed further in conse-quence of such overloading of the liver’scapacity passes into the bloodstream andis finally excreted in the urine via the kid-neys.

The causes of overloading of the func-tional capacity of the liver may be listed asfollows:� Increased degradation of haemoglobin

in:– haemolytic anaemia– pernicious anaemia– intravasal haemolysis, e.g. as a

result of intoxications, infectious dis-eases, or transfusion accidents

– polycythaemia– reabsorption of large extravasations

of blood

44

Urobilinogen

� Liver tumours (depending on their sizeand location)

� Incomplete obstructions of the bileducts (depending on the degree ofparenchyma cell damage)

In viral hepatitis in particular urobilino-genuria is very often encountered, whilethe cardinal symptom proper, namelyjaundice, is mostly absent.

Bypassing of the liverIn certain pathological conditions, e.g. inliver cirrhosis, the influx of portal veinblood and therefore also of urobilinogento the liver is reduced. Part of the uro-bilinogen then bypasses the liver and isexcreted in increased amounts in theurine.

The causes of liver bypass include thefollowing conditions:� liver cirrhosis with portal hypertension� portal vein thrombosis� occlusion of the hepatic vein

� Increased formation of urobilinogen inthe intestine due to:– pronounced constipation– enterocolitis– ileus– increased fermentation processes

� Increased urobilinogen formation andreabsorption in bile tract infections,e.g. in cholangitis.

Impairment of the functional capacity of the liverLiver diseases exert an adverse effect on its functional capacity. The urobilinogencoming in through the portal vein can no longer be completely processed andappears in increased amounts in theurine.

The functional capacity of the liver may bereduced in the following situations:� Viral hepatitis (except in very severe

forms or for a short time at the peakof the illness)

� Chronic hepatitis and liver cirrhosis(depending on the degree of damageto the parenchyma cells)

� Toxic liver damage (e.g. due to alco-hol, fungal poisons, organic solvents,medicines, and toxins produced in thecourse of infections or sepsis)

� Congestion of the liver (e.g. after acardiac infarct, acute heart failure, orcardiac insufficiency)

� Liver hypoxia (e.g. after severeanaemias or intoxications with carbonmonoxide)

45

Urobilinogen

Absence of urobilinogen in the urineUrobilinogen is absent in the urine in sit-uations comprising failure of bile produc-tion in the liver cells, disturbances of bilesecretion into the intestine, and absenceof bilirubin reduction in the intestine, eventhough a severe disease may be present.

Possible causes of failure of urobilinogenformation:� complete obstruction of the common

bile duct in the absence of a bile tractinfection

� complete stoppage of bile productionin the liver (very severe viral hepatitis,severe toxic liver damage)

� absence of intestinal flora (physiologi-cal in newborn babies, rarely observedafter intensive antibiotic therapy)

46

Bilirubin

False-negative results:� prolonged standing of the urine,

particularly in direct sunlight, leads tooxidation of the bilirubin.

False-positive results:� medicines that color the urine red

or that are themselves red in an acidmedium, e.g. phenazopyridine.

Clinical significanceAs a result of conjugation (esterification)with glucuronic acid bilirubin becomeswater-soluble and therefore susceptibleto excretion by the renal route. The biliru-bin present in urine is always conjugated(direct) bilirubin.

In all pathological processes that increasethe concentration of conjugated bilirubinin plasma, the excretion of bilirubin inurine can reach considerable levels. Con-jugated bilirubin is found in the following

Test principleThe test reaction is coupling of the bili-rubin with a stable diazonium salt (2,6-dichlorobenzenediazonium fluoroborate)in an acid medium of the test paper. Ared-violet azo dye is formed, causing acolor change to violet.

Reference rangeAdults below 3.4 µmol/L (below 0.2 mg/dL).

Practical detection limitThe practical detection limit in urine free from ascorbic acid lies at 9 µmol/L (0.5 mg/dL). In favourable cases as littleas 3–7 µmol/L (0.2–0.4 mg/dL) may givea positive reaction.

Sources of errorThe sensitivity is degraded by large amounts of ascorbic acid in the urinespecimen.

47

+ -

Bilirubin

Cl

Cl

Azo dye (red-violet)

Diazonium salt

BF4 + BilirubinN N

Test principle

Acidmedium

Fig. 18: Principle of the bilirubin test

Bilirubin

Bilirubin

situations as a result of its increased pas-sage from the liver into plasma:

� increased intracanalicular pressure dueto an extrahepatic or intrahepaticobstruction

� periportal inflammation or fibrosis� swelling or necrosis of the liver cells

Bilirubinuria can be encountered in thefollowing clinical conditions:

Damage to the liver parenchymaThis is the commonest cause of bilirubi-nuria. The cell membrane permeabilityincreases and conjugated bilirubin appearsin the blood and via the kidneys in urine:� acute and chronic viral hepatitis� alcoholic hepatitis� fatty liver hepatitis� liver cirrhosis� toxic liver cell damage

Bilirubin excretion disturbancesWhen conjugated bilirubin can no longerbe secreted into the bile ducts as a result of an excretion disturbance of the liver,various amounts of it pass through thecell membranes or via the lymph intoblood, depending on the severity of thehepatic disturbance, and escape via thekidneys into urine:� the Dubin-Johnson syndrome� Rotor’s syndrome� intrahepatic cholestasis and drug

icterus� icterus of pregnancy� cholestasis occurring after infectious

diseases

Impedance of bile flowIf bile flow is impeded within or outside theliver or interrupted altogether, the result ischolestasis and with it a rise in conjugatedbilirubin in the serum and bilirubin ex-cretion in urine:� cholangitis� cholangiolitis� cholecystitis� intrahepatic bile duct carcinoma� extrahepatic obstructive jaundice due

to stone occlusions, tumours, andstrictures

Absence of bilirubinuria inhyperbilirubinaemiaDiseases in which only unconjugatedbilirubin is increased in the serum pro-ceed without bilirubinuria, because un-conjugated bilirubin is not excreted by the renal route. The cause may be anoversupply of bilirubin in the liver cells ora disturbance of uptake or conjugation:� haemolytic jaundice� jaundice of the newborn� Gilbert-Meulengracht disease� Crigler-Najjar syndrome

On account of the differentiated liverdiagnostics in serum, detection of bili-rubin in urine has now lost much of itsformer significance.

48

Blood (erythrocytes/hemoglobin)

acid concentrations have virtually noinfluence on the test result.

Intact erythrocytes are lysed on the testpaper and the haemoglobin released setsoff the color reaction. Visible green pointsare formed. In contrast, haemoglobin dissolved in the urine (erythrocytes inlysed form) leads to the development of auniform green color.

Reference range0–5 erythrocytes/µL.

Detection limitThe practical detection limit for intact ery-throcytes is about 5 erythrocytes/µL andfor haemoglobin the amount correspon-

Test principleThe test is based on the peroxidativeaction of haemoglobin or myoglobinwhich catalyzes the oxidation of the colorindicator TMB by an organic hydroper-oxide (2,5-dimethylhexane-2,5-dihydro-peroxide) to give a blue-green dye whichon the yellow test paper causes a co-lour change to green. High sensitivity isachieved by the addition of an activator to the reagent mixture.

The risk of interference from ascorbic acidknown for this oxidation reaction hasbeen eliminated; the test area has aniodate-impregnated mesh laid over theactual reagent paper, which oxidizes anyascorbic acid present. Even high ascorbic

49

Blood

OOH OOH

CH3 CH3

3,3',5,5'-Tetramethylbenzidin2,5-Dimethylhexan-2,5-dihydroperoxid

NH2 + H2NCH3 CH2 CH2C CH3C

OH OH

CH3 CH3

CH3 CH2 CH2C CH3C

Test principle

+ dye (blue-green)

CH3 CH3

CH3 CH3

HemoglobinMyoglobin

Fig. 19: Principle of the test for blood (erythrocytes/hemoglobin)

Blood


ding to around 10 erythrocytes/µL. Thepractical detection limit of the test reach-es the limit of the normal range.

SpecificityThe test is specific for haemoglobin andmyoglobin. Other cellular constituents ofthe urine, such as epithelia, leukocytes,and spermatozoa, have no effect. Therarely encountered green coloration ofleukocyte-containing urine specimens isprobably attributable to haemoglobin.

Sources of error� In test strips from Roche the interfer-

ence due to ascorbic acid (vitamin C)in the detection of blood has beenwidely eliminated so that ascorbic acidhas virtually no influence on the testresults.

� False-positive results can be obtainedif the urine contains residues ofstrongly oxidizing cleaning agentsfrom the container.

Evaluation

ErythrocytesThe observation of individually separatedto closely set green dots on the test paperpoints to the presence of intact erythro-cytes.

At higher concentrations the dots may beso close together that the test areaappears almost uniformly green. Dilutionof the urine 1:10 or 1:100 with 0.9% (phys-iological) saline and repetition of the testwith another strip then makes it possibleto decide whether intact erythrocytes orfree haemoglobin is present.

A finding of 5–10 erythrocytes/µL re-quires repeated checks on the urine, and if it is obtained again must be clinicallyclarified.

HaemoglobinA homogeneous green color of the testarea points to the presence of freehaemoglobin or lysed erythrocytes, or tothe presence of myoglobin.

A weaker green color, as a first sign of apositive reaction, requires a repetition ofthe test with a fresh urine specimen. Thissecond test may reveal, inter alia, intacterythrocytes which at the time of the firsttest had already become haemolyzed.Persistence of the finding requires a clin-ical clarification in all cases.

50


Clinical significanceHaematuria, excretion of erythrocytes inthe urine, is encountered in many patho-logical conditions, and careful clarifica-tion of its cause is therefore absolutelynecessary.

This applies both to microhaematuria andto macrohaematuria, red coloration of theurine perceptible to the naked eye due tothe presence of more than 0.5 mL bloodper litre of urine, corresponding toapproximately 2500 erythrocytes per µL.

The principal causes of haematuria areconditions relating to the kidneys and theurogenital tract (Fig. 20).

In the event of a weakly positive haemo-globin reaction the cause may also besimply heavy physical exertion. This canbe easily excluded from the anamnesis.

Partial haemolysisPartial haemolysis of erythrocytes presentin the urine leads to the appearance onthe test area of individual green dotsagainst a diffuse green background. Anexact assignment of the comparison coloris then impossible, because the degree ofhaemolysis can be very variable as afunction of age, concentration, and pH ofthe urine. A repeat test with a fresh urinespecimen is indicated.

51

Important renal and postrenalcauses of haematuria

Glomerulonephritis Renal tumuor

Pyelonephritis

Ureteral stone

Cystitis

Prostata adenoma

Kidney stone

Ureteral tumour

Bladder carcinoma

Bladder stone

Fig. 20: Important renal and postrenal causes of haematuria


Stone formationApproximately 1–3% of the populationsuffers from urolithiasis or is at a risk ofurolithiasis. Oxalate-containing stones(about 60 %), phosphate-containing sto-nes (about 20%), and uric acid calculi(about 25%) are particularly frequent.Most of these patients also exhibit hy-peruricaemia. Men are affected by thecondition much more often than women.Stones in the efferent urinary tract as a rule provoke acute colic-like pains,though the initial stage of stone forma-tion may be completely painless. Detec-tion of haematuria is then often the firstsymptom.

TumourThe possibility of a tumour should alwaysbe suspected until the cause of thehaematuria has been clarified.

Microhaematuria is decisive for earlydetection of malignant tumours in the kid-neys, the efferent urinary tract, and thebladder. Determination of this symptom istherefore very important, since tumoursoften remain painless for a long time.

GlomerulonephritisIn the presence of glomerulonephritishaematuria acts as a detectable leadingsymptom in approximately 90% of thecases. Proteinuria and hypertension arealso often observed in addition. Glomeru-lonephritis is mostly encountered in chil-dren and in adults under the age of 30.

Most forms of glomerulonephritis can beattributed directly or indirectly to anearlier infection. The important forerunnerdiseases of glomerulonephritis and otherglomerular damage may be listed as fol-lows:� sore throat, chronic tonsillitis� colds, influenzal infections, pneumonia� scarlet fever, diphtheria, measles,

mumps� sinusitis, otitis� skin infections, particularly in children� lupus erythematosus� relapsing dental foci� chronic appendicitis� endocarditis lenta� polyarteritis nodosa

Elimination of these typical forerunnerconditions is necessary to prevent thesubsequent development of glomerulardamage. The possibility of a renal involve-ment is checked most easily by the deter-mination of microhaematuria.

PyelonephritisAccording to clinical data the incidence ofpyelonephritis is estimated at 5–8%. Thepopulation groups affected most often arewomen and older men. Haematuria ispresent in one-third of these patients.

52


occurs as a rule from plasma haemoglo-bin concentrations of around 60 µmol/L(100 mg/dL).

Myoglobinuria is generally due to muscu-lar injury or muscular necrosis, when the myoglobin level in plasma exceeds9–12 µmol/L (15–20 mg/dL).

Since haemoglobin and myoglobin aredifficult to distinguish in a urine specimen,some of the positive test results obtainedafter heavy physical exertion must beattributed to myoglobinuria.

The causes of haemoglobinuria or myo-globinuria are as follows:� severe haemolytic anaemia� severe intoxications� severe infectious diseases� burns� intensive physical exertion, e.g. in

training athletes� muscle injuries� progressive muscle diseases

Haemorrhagic diathesesThe following causes of haemorrhagicdiatheses come into consideration:� treatment with anticoagulants� haemophilia� coagulopathies� thrombocytopenia

Further diseases� urinary tract infections (cystitis, uro-

genital tuberculosis)� toxic and hypoxic damage and degen-

erative changes in the glomeruli� papillary necrosis� trauma to the kidneys and urinary

tract� renal infarct� renal cysts� gouty kidney� renal congestion in the presence of

right-ventricular failure� hypertension in the presence of vas-

cular renal involvement� diabetes mellitus� lupus erythematosus

Haemoglobinuria and myoglobinuriaIn contrast to haematuria, in which intacterythrocytes are excreted, in haemo-globinuria the urine contains free haemo-globin. This appears in the urine whenerythrocytes have been broken downwithin the vascular system. Followingintravasal haemolysis the haemoglobinpasses into the urine as soon as the hap-toglobin-binding capacity of the plasmaand the tubular reabsorption capacity forhaemoglobin have been exceeded. This

53

The test strip sieve

differential diagnostics or subjected to abacteriological examination.

If the test strip results turn out to be neg-ative and there is nothing in the patient’smedical history or clinical picture to raisesuspicion of a pathological process, thelaborious and time-consuming micros-copy and bacteriology need not be carriedout.

On average every other sample is thusexcluded from subsequent examination ofthe sediment, resulting in an appreciablerationalization of the urinalyses.

The reliability of the “test strip sieve” inpicking out pathological specimens is

Principle of test strip sieveSeveral comparison studies have shownthat pathological changes in the urine canbe detected more reliably with the aid ofmultitest strips than by examinations ofthe sediment. This led to the developmentof the “test strip sieve” concept, a step-wise procedure in which the two exami-nation methods are efficiently combined.

The urine specimen is first routinely inves-tigated with test strips for leukocytes,blood, protein, nitrite, and a pH greaterthan 7. If at least one of these parametersis found to be positive, the urine is desig-nated as “microscopically relevant.” Thesespecimens are then immediately checkedfor sediment constituents important for

55


All results negative, no suspicious signs in themedical history or the clinical picture:

no further urinalysis necessary.Microscopic examination of the urine can thus

be avoided in about half of the cases.

pH>7NitrituriaProteinuriaHaematuriaLeukozyturie

One or more of the test strip results are positive:

indication for targeted microscopicand/or bacteriological examination

of the urine.

Principle

ìFilterin g out” of microscopically relevant urine specimens

Test-strip finding

Fig. 21: Rational urine diagnostics according to the Òtest strip sieve ” concept

3


approximately 95%, while in the case ofsediment analyses only about 80–85% ofrelevant urine specimens can be recog-nized as conspicuous.

The “test strip sieve” does not detect var-ious types of crystalluria and hyalinecasts, but the diagnostic informative pow-er of these parameters is low.

Microscopy/test strip comparisonTest strips allow a direct or indirect detec-tion of the microscopic elements listed inFig. 22.

For red and white blood cells the twomethods are in good agreement, as longas the cells are still intact and micro-scopically detectable.

With increasing lysis low or false-negativeresults are obtained in the microscopicexamination.

Cell lysis is accelerated by the followingconditions:� low specific gravity or osmolality of

the urine� high pH (pH >7)� long standing time of the urine

(>2 hours)� high room temperature

In contrast, the haemoglobin from ery-throcytes and the esterase from leuko-cytes are still detectable with urine teststrips after several hours. Moreover, thecentrifugation of the urine specimen nec-essary for subsequent microscopy leadsto an appreciable loss of the cells.

The concentration values on the test colorscales and the reflectance photometricprintouts of the results (erythrocytes/µL,leukocytes/µL) for test strips are based oncomparisons with chamber counting. Theconversion into numbers of cells per highpower field is inexact, because sedimentexamination has still not been standard-ized and its result is influenced by variousfactors such as the sample volume or theduration of centrifuging.

56

Test strips Microscopic elements

Blood Erythrocytes, erythrocyte castsLeukocytes Leukocytes, leukocyte castsProtein Granular casts, waxy castsNitrite Bacteria

Fig. 22: Microscopic clarification of pathological test strip findings

Microscopic assessment of the sediment

Working up� 10 mL volumes of well-mixed urine

are filled into centrifuge tubes with atapered bottom and centrifuged for 5 minutes at about 400 g (1500 revo-lutions per minute with a radius of 15 cm)

� The supernatant is decanted in a single operation, without swirling upthe sediment or entraining it into theliquid phase

� The sediment is then resuspended inurine running back down the tubewalls

Performance of the examination� A small droplet (about 20 µL) of the

sediment is placed in the middle of aclean microscope slide.

� A cover slip is then placed on it,avoiding the formation of air bubbles.

� Using a ×10 objective, the sample ischecked for casts parallel to theedges of the cover slip.

� Using a ×40 objective, at least 10fields are inspected.

� The results are documented as fol-lows:

Urinalysis with test strips often requiresan additional microscopic examination ofthe sediment in order to support the diag-nosis. In the following indications addi-tional examination of the sediment is nec-essary to supplement the test strip result:� one or more pathological test strip

findings� the patient exhibits symptoms of a

kidney or efferent urinary tract disease� course control of a kidney or efferent

urinary tract disease� determination of a suspicious result.

A cell atlas showing the most importanturinary sediment constituents is includedin the Appendix to this brochure.

PrincipleSediment analysis consists of a micro-scopic examination of the precipitate of a centrifuged specimen of native urine, asa rule using ×10 and × 40 objectives. Theelements investigated are cells, casts, andindividual microorganisms. It should benoted that sediment analysis is not stan-dardized and does not yield valid quanti-tative results.

Test materialMidstream urine collected not more than2 hours earlier, without the use of preser-vatives. The concentrated morning urineis optimal, because erythrocytes andleukocytes are readily haemolyzed inhypotonic urine.

57

Cells

(+) 0–1 perfield (correspondsto about 0,3 µL)

+ 1–5++ 6–15+++ 16–50Abundant > 50


ResultIf urinalysis with test strips was carriedout at the same time, the results are inter-preted in combination and documentedas a joint finding.

ErythrocytesRound discs without nuclei (diameter 7–8µm), without granules, with a doubly-con-toured margin; in hypertonic urine theyare shrunken into a thorn apple form;after emergence of their haemoglobinthey fade to pale shadows. Deformed(dysmorphic) erythrocytes are ofglomerular origin and are indicative of thepresence of a kidney disease.

Sources of error: Possible confusion withfat droplets or yeast cells (smaller, oval, often germinating).

Reference interval: 0–5 per field of view, >30% of dysmorphic erythrocytes points to their glomerular origin.

LeukocytesAlmost exclusively granulocytes (diameter10–12 µm).Sources of error: In the case of women

spontaneous urinegives up to 40% offalse-positive resultsdue to vaginal contam-ination.

Reference interval: 0–5 per field of view.

Epithelial cellsPavement or squamous epitheliumcells always originate from the urethra orthe external genitals and are regarded ascontamination.

Transitional epithelium cells are small-er than pavement epithelium cells, oftenhave tail-like processes, and come fromthe efferent urinary tract.

Renal epithelium cells are the only onesof diagnostic significance. They comefrom the tubules and resemble leuko-cytes; they are distinguished by their largeround nuclei.

CastsProtein-containing cylindrical castsfrom the renal tubules, with a diameter of15–50 µm.

Hyaline casts are transparent, colorless,and structureless formations of Tamm-Horsfall protein, a mucoprotein secretedby the distal tubules. They often appear inthe urine following physical exertion, pro-longed standing, or fever, and they haveno diagnostic significance.

Granular casts are observed most oftenin the presence of chronic glomeru-lonephritis. Droplets of plasma proteins orfragments of lysed cells are included inthe matrix.

58


ArtefactsRecognition of artefacts is essential ifincorrect interpretations are to be avoid-ed.

Fat droplets are as a rule due to contam-ination with ointments, residues of sup-positories, or catheter lubricants.

Crystals are usually treated as artefactsbecause they are only formed pH-dependently in cooled urine on standing.Diagnostic significance is attributed onlyto the extremely rare crystals of cystine(colorless hexagonal plates), leucine (yel-low-brown spheres with radial banding),and tyrosine (clusters of fine, colorless,shiny needles).

Fungi (most often yeasts) are usually theresult of contamination; fungal infectionsare rare.

Starch grains are round to oval, variablein size, and exhibit concentric layering.They originate from cosmetic powders.

Fibres are frequently observed as con-taminants.

Pollen grain may be confused with wormeggs.

Erythrocyte casts are made up of eryth-rocytes embedded in a homogeneousmatrix. They point to a renal origin of thehaematuria.

Leukocyte casts similarly point to arenal origin of the leukocyturia, which canbe differentiated from a leukocyturia dueto cystitis or a vaginal discharge.

Epithelial casts consist of desquamatingtubular epithelium and are indicative ofischaemically or toxically determined tu-bule cell necroses. With time they degen-erate to granular and finally wax-likecasts.

Renal insufficiency casts are 2–6 timesas wide as the other cylindrical casts. Theyare formed in dilated tubules or in collectingtubules when the flow of urine has beenstrongly slowed down.

Microorganisms Bacteria can only be detected and theresult documented as a “yes” or “no.”Simultaneous observation of leukocyturiais indicative of an infection, otherwise thepossibility of contamination should beconsidered.

Trichomonads (diameter 10–30 µm) arebest observed live in very fresh urine bytheir erratic motion.

Worm eggs or echinococcal con-stituents are rarely observed in the urinein Central Europe, in contrast to the trop-ical countries.

59

Urine culture

Urine is normally a virtually sterile bodyfluid, but it may serve as a very goodnutrient medium for many bacteria.

DiagnosticsThe evidence for a urinary tract infectioncan be based on a test strip reaction (apositive nitrite test or leukocyturia) or onthe outcome of microscopic examinationof the sediment (leukocytes, bacteria).

Pre-packed immersion nutrient media aresuitable for primary culture and for micro-bial count determinations of gram-posi-tive and gram-negative bacteria, and alsoas a medium for transport between thedoctor and the test laboratory. CLED agarcan be used for growing all organisms,and it is particularly good for urinary tractpathogens. MacConkey agar largely sup-presses the growth of gram-positives withthe exception of enterococci. Proliferationof Proteus is largely suppressed on boththese agars. Other nutrient media are alsoavailable, e.g. for selective growth ofPseudomonas. Gonococci, mycobacteria,and other relevant organisms do not grow.

Sample materialMidstream first morning urine.

AnalysisThe nutrient medium carrier is dipped infresh urine in a sterile container to adepth such that the agar layer is com-pletely moistened. If the sample volume issmall, the agar layer is carefully mois-tened all over.

� The excess urine is allowed to flow offthe medium carrier; the last few dropson the lower edge of the carrier heldvertically are removed by suctionusing a swab.

� The nutrient medium carrier is nextplaced back in its tube and incubatedfor 16–24 hours at 35–37°C.

60

Urine culture

61

1000/mL 10,000/mL 100,000/mL 1,000,000/mL

Contamination Doubtful range Infection

(Midstream urine)Catheter or bladder puncture urine: a count of less than 10,000 bacteria per mL can already be indicative of an infection in this case.

Fig. 23: Microbial counts on MacConkey agar

Repetition of the testis recommendedbecause thesecounts occur inchronic urinary tractinfections, but theycan also appear inmidstream urine ascontaminants.

The urine sediment must beexamined. In women highmicrobial counts can some-times be due to externalcontamination, e.g. due tovaginal discharge or vagini-tis, and the urine sedimentcan then show increasednumbers of pavement epi-thelia without an increasein leukocytes. A diagnosisof infection is therefore reli-able only when the testurine has been obtained bycatheterization or by blad-der puncture. Subsequentidentification of the organ-ism and a determination ofits antibiotic sensitivity arenecessary.

Urine culture

Interpretation� If each side of the nutrient medium

carrier shows <10,000 organisms/mL,the specimen has most probably beencontaminated and the result is notsignificant.

� The bacteriuria is significant whenboth sides of the carrier give a countof over 100,000 organisms/mL.

� This reference value applies whenonly one organism is present; if thereare two or more species the bacteri-uria is again usually due to contami-nation.

Further procedure� The nutrient medium carriers must

be dispatched to the test laboratorywithin 24 hours.

� As a rule the frequently encounteredlocal pathogens such as enterobacte-riaceae, non-fermenting gram-nega-tive bacilli, staphylococci, streptococci,and fast growing Candida strains areroutinely cultured. Less frequentmicroorganisms, such as Mycoplasma,Mycobacteria, and anaerobes are cul-tured only when this is speciallyrequested. Resistance tests are donein the usual way.

Remark� The nutrient medium carriers must be

kept in unopened tubes at 15–25°Cuntil the expiry date. They must not be frozen. Carriers showing signs ofmould or bacterial growth must not beused. Water of condensation does notinterfere as long as the nutrient layeris not appreciably shrunken.

62

Urine cytology with Testsimplets

EvaluationIt is best to start screening the prepara-tions at ×100 magnification and then toassess specific suspect cells or cell clus-ters at ×200 to ×400 magnification or at×1000 magnification using oil immersion.

The vital staining means that stained cellsappear at their natural size, so – by con-trast to other techniques – details such asthe nuclear structures and nuclear mem-branes in particular are extremely clear.

Clinical significanceTestsimplets permit extraordinarily gooddifferentiation and classification of nu-clear structures, nuclear membranes,chromatin networks, and nucleoli as wellas structures in the cytoplasm.

Urinary cytodiagnosis is helpful in:� all forms of micro- and macrohaemat-

uria� treatment-resistant cystitis� cystalgia� dysuria of unclear origin� follow-up after urothelial tumour

operations� early identification and follow-up of

bladder cancer

Assessment of the degree of malignancyis carried out in exactly the same way aswith conventional staining techniques.

Testsimplets*) are ready-to-use stain-coated microscope slides which produceexcellent color differentiation of cells inbody fluids for microscopy and in cytolog-ical screening of urine. Testsimplets per-mit rapid differential staining of suspectedcancerous cells in urinary sediment andreplace the time-consuming Papanico-laou and Pappenheim staining proce-dures.

The simple, clean procedure and rapidstaining with standard stains make Test-simplets easy to use in the doctor’s officeor hospital.

ProcedureThe method of working up the urine issimilar to that used when preparing nor-mal urinary sediment:1. Centrifuge the urine at 3000 rpm for

approx. 10 minutes2. Carefully decant all the supernatant3. Resuspend the sediment in 3 drops of

physiological saline4. Put 1 drop of this suspension in the

middle of one of the enclosed coverslips and lay it on the color field

5. The staining process is complete after5–10 minutes

6. The preparation can then be examined

The preparation can be evaluated up to 5 hours after staining if kept at room tem-perature.

63

*) Distributed by: Diagonal GmbH & Co. KGHavixbecker Straße 62, D-48161 Münsterwww.diagonal.de, [email protected]

Automated Urinalysis

Instrumental urinalysisBecause of their ease of use, high sensiti-vity and specificity, Combur-Test urinetest strips permit rapid and reliable con-clusions about pathological changes inthe urine. However, it is not really possibleto standardize visual evaluation of urinetest strips, and a number of environmen-tal factors such as � differences in light conditions at the

workplace� strongly colored urine samples� individual differences in color differen-

tiation ability of users� declining concentration when examin-

ing long series of samples, and� differences in the accuracy of compli-

ance with the specified test strip reac-tion time

can have a negative effect on the qualityof the result.

Instrumental evaluation of urine test stripsvirtually eliminates the above factors andguarantees a rapid, standardized meas-urement and immediate reliable docu-mentation of the result.

Urinalysis systems can be divided into 3 categories:

Instruments intended for single measurementsOne test strip is inserted at a time, manu-ally. The test strip is measured automati-cally, and the result is delivered afterabout 1 minute. The test strip then has tobe removed manually.

Semi-automatic urinalysis systemsTest strips can be inserted manually atshort intervals. Transport, measurement,and disposal of the used test strips into an

64

Urisys 1100ParameterSpecific gravity 610 nmpH 610 nm / 565 nmLeukocytes 565 nmNitrite 565 nmProtein 565 nmGlucose 565 nmKetone 565 nmUrobilinogen 565 nmBilirubin 565 nmErythrocytes 610 nmCompensation 565 nm

Table 3: Wavelengths


improved accuracy near the limit of detec-tion.

In calculating the result, a correction forinterference by the intrinsic color of theurine is made by measuring a blank fieldon the test strip (compensation field). Inaddition, the result of the Specific Gravitytest is automatically corrected if the pH ishigh.

Although urinalysis systems using reflec-tance photometry evaluate the test fieldcolor changes with high precision, it is notpossible to completely eliminate all differ-ences in the composition of the samplematerial which could have an effect oncolor development, so urinalysis systems –unlike instruments for the measurementof blood glucose or Reflotron – only yieldsemi-quantitative results.

in-built container are automatic. Theresults are automatically saved in thememory and printed out.

Fully automatic urinalysis systemsManual dipping and insertion of the teststrips is not necessary. The urine samplesare applied from sample tubes using arotor or rack. Sample identification, thetest procedure and disposal of the usedtest strips into an in-built container arefully automatic. The results are automati-cally saved in the memory and printed out.

Urinalysis systems evaluate test strips byreflectance photometry using selectivelight-emitting diodes with a wavelengthand measurement time tailored exactly tothe chemical reaction and color develop-ment of the test field concerned. Compar-ed with visual assessment, this produces

65

cobas u 411 system Urisys 2400

620 nm 650 nm620 nm / 555 nm 620 nm / 555 nm555 nm 555 nm555 nm 555 nm620 nm 555 nm555 nm 555 nm555 nm 555 nm555 nm 555 nm555 nm 555 nm620 nm / 555 nm 620 nm / 555 nm555 nm 555 nm

4


As well as correct determination of thetest strip result with the objective ofachieving a high level of standardization,urinalysis systems must fulfil the data-processing requirements of the laboratoryenvironment. The urinalysis systems sup-plied by Roche can be connected to bar-code scanners for automatic sample iden-tification and to external printers to printthe findings, and the results of the meas-urements can be transferred to the labo-ratory computer system or PC. Fully auto-matic urinalysis systems such as Urisys2400 and semi-automatic systems such asMiditron M and Miditron Junior II havealready proved themselves over a periodof years in the hospital laboratory. As alogical development of Miditron M a new

system, Urisys 1800 was launched in 2004and received an update to cobas u 411system mid of 2007.

The compact Urisys 1100 system enableseven the medical practice, the small hos-pital laboratory or hospital ward to makeuse of the advantages of instrumentalurinalysis.

66

Measuring Head (Sensor)

Detector

orange

Test strip

Scheme

green

Fig. 24: Measuring Head (schematic)


Finally, the system compares the reflec-tance values with the defined range limits(reflectance values that are programmedin the analyzer for each parameter) andoutputs a semi-quantitative result (6). Re-sults can be printed out or transferred tothe laboratory computer system.

Before each measurement the optical sys-tem is tested and corrected for variationsin LED brightness and detector sensitivityusing internal reference settings. The cor-rect positioning of the test strip under theoptical system is checked during themeasurement. If the strip is not in the cor-rect position the result is not printed out,and the instrument instead asks for themeasurement to be repeated.

The LED (1) emits light of a defined wave-length on to the surface of the test pad (2)at an optimum angle. The light hitting thetest zone is reflected from the surfacemore or less intensely depending on thecolor produced on the test pad, and ispicked up by the detector (3), a photo-transistor positioned directly above thetest zone. The phototransistor sends ananalogue electrical signal to an A/D con-verter (4), which changes it to digital form.The microprocessor (5) then converts thisdigital reading to a relative reflectancevalue by referring it to a calibration stan-dard.

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Determination of measured values

1

2

3

4

5Detector

Analogue-digital converter

Test pad surface

Microprocessor

6 Result

LED

Scheme

Fig. 25: Reflection photometry (schematic)


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Urisys 1100Urisys 1100 is a compact, time-savingurinalysis system for reflectance-photo-metric measurement of individual teststrips of the Combur-Test line. The systemtest strip for Urisys 1100 is Combur10TestUX with 10 urine parameters and an addi-tional field for compensating for the colorof the urine. Urisys 1100 can also measureCombur7Test and Combur5Test urine teststrips without compensation pad1).

Operation of Urisys 1100 is perfectly simple: Just dip the test strip in the urinesample, place it on the movable loadingtray, and press the start button. The sys-tem does the rest. After 55 seconds itreads the individual fields on the test stripone after the other and prints out theresult on the integrated low-noise thermalprinter. There is the option of sending theresults through a serial port to a PC orlaboratory computer system. The wholemeasuring cycle takes about 70 seconds,so it is possible to measure approx. 50samples per hour.

When carrying out the measurementsUrisys 1100 automatically assigns eachsample a serial number, but there is alsothe option of inputting patient numbers

using a bar-code scanner or a PC key-board. The printout of the results includesa heading, the serial number, the date andtime, and patient ID. Abnormal results areflagged and are thus immediately recog-nizable. The results can be printed out inconventional, SI, or arbitrary units. Thenumber and sequence of the parameterson the printout can be selected at will 2)

and, even when printing out immediatelyafter the measurement, it is possible tochoose between one and two copies.Urisys 1100 can store up to 100 readingswith patient data. There are also variousoptions available for later or multipleprintouts.

All system settings are accomplishedusing the function keys in associationwith text shown on the display, which isavailable in 5 languages. The user instructions areclear and self-explanatory. Inbuilt check-ing functions inform the user of any operating or system errors. WhenCombur10Test UX strips are used, Urisys1100 automatically requests a weekly cal-ibration with Control-Test M. Calibration isjust as quick and easy to carry out as themeasurement itself.

When a strongly alkaline urine sample isbeing measured, Urisys 1100 automatical-ly corrects the result of the specific gravi-ty test field. When the urine sample has astrong intrinsic color, automatic colorcompensation is performed 3). Measure-ment sensitivity can be fine-tuned by

1) In some countries Combur7Test andCombur5Test are not available or are notoffered for use with Urisys 1100.

2) not available in the U.S. version.3) only when Combur10Test UX is used.


69

gradually adjusting the factory set limitsto suit the user’s individual requirements.2)

Inserting a new roll of paper and cleaningthe device is simplicity itself. Just removethe loading tray and clean it under run-ning water. Load the roll of paper and close the printer cover – Urisys 1100 isready to perform the next measurement.

Urisys 1100 can evaluate the well-provenCombur-Test urine test strips. The proce-dure is easy, user-friendly, time-savingand standardized. Because the system isso simple to operate and provides a num-ber of software options, it is ideal for med-ical practices, small laboratories and hos-pital wards.

The benefits at a glance

� Handy, compact instrument for measuring individual test strips. Urisys 1100 delivers standardizedresults and virtually excludes sources of error associated with visual evaluation.

� Easy to use: Place the test strip on the loading tray and press the startbutton. The system does the rest –quietly and efficiently.

� Optimized procedure: Immediate automatic documentation of results –option of printing or sending them toa PC or laboratory computer system.

� Reliable results: Can measure thehigh-quality Combur10Test UX teststrip.

� Useful computer interface: Urisys 1100has a serial interface for connection to a PC or laboratory computer sys-tem. An optional bar-code scanner orPC keyboard may also be used toinput patient data.

� Efficient in daily routine: Very simpleoperation, fast results, reliable docu-mentation, changing paper and clean-ing done in a matter of seconds.

� Interactive user guide on CD-ROM:Videoclips explain procedures fromfirst-time startup to maintenance.


70

cobas u 411 systemcobas u 411 system is a semi-automaticurinalysis system for reflectance-photo-metric evaluation of Combur10Test M urinetest strips.

Measuring urine samples with cobas u411 system is perfectly simple: Dip teststrips in urine and place them on theinsertion tray. The system will detect theirpresence and transport them to the meas-uring position on a 6-second work cycle.Following an incubation time of approx.60 seconds each test strip is measuredand then placed in the inbuilt waste con-tainer. The high throughput of max. 600strips per hour means that even largenumbers of samples can be processedquickly and efficiently. System memorycan accommodate up to 1000 completetest data records.

cobas u 411 system has a large intuitiveLCD touch-screen that grants directaccess to various software features,enabling the user to call up various sys-tem functions and adjust settings quicklyand conveniently. cobas u 411 systemsupports quality control of test strip read-ings by allowing the name, batch numberand standard values of control urines tobe input and saving the results in a sepa-rate 300-position memory reserved forcontrols (100 per control level).

Sample and control results can be printedout via the integral thermal printer withoptimized paper format (112 mm wide),

sent to a laboratory computer system viathe integral port (ASTM standard inter-face protocol) or saved to USB stick. Inaddition, the inbuilt USB port can be usedto save calibration results and laboratory-specific system settings.

Ports are provided for connecting a bar-code scanner and a Sediment Terminal. A ST allows sediment findings to be inputin parallel to the test strip measurements,so that a second person can carry on withtime-intensive microscopic examinationsat the sediment workstation while the oth-er samples are being measured in thecobas u 411 system. The complete urinal-ysis finding is documented as alreadystated above.

Thanks to its extreme user-friendlinessand superior data management, cobas u411 system is the right choice to carry out efficient routine urinalysis in laboratorieswith a urine sample throughput of 50 –100samples per day and more.


71

� Ports for bar-code scanner and bidi-rectional connection to the laboratorycomputer system

� Sediment Terminal connectivity forinputting microscopic findings

� Inbuilt USB port for optionally savingsample results and calibrations to disk

� Numerous setting options for optimaladjustment to the individual operatingsituation and laboratory environment


� Semi-automatic urinalysis system for measuring Combur10Test M

� Continuous loading of dipped teststrips without the need to keep to a strict timing regime

� Easy user guidance through large LCD touch screen

� Separate data handling for quality control measurements

� Support of lot numbers and expirydate of the test strips and the calibra-tion strips


Urisys 2400Urisys 2400 is a fully automated urinalysissystem for reflectance-photometric evalu-ation of Urisys 2400 Cassette test stripsincluding the parameters pH, leukocytes,nitrite, protein, glucose, ketones, urobili-nogen, bilirubin, erythrocytes and color,as well as specific gravity (refractometry)and clarity via physical determination.

Urisys 2400 provides enhanced walk-away capability for medium to high vol-ume laboratories with typically > 100 urinesamples per day.

It is the first urinalysis system with aninnovative cassette providing the userswith highly convenient reagent handling,and with Roche standard racks for com-mon sample handling. Because all stepsin the operation, from pipetting the urinesample onto the test strip to output of thetest results, are completely automatic,manual handling of the samples and teststrips is reduced to a minimum.

The samples are placed on the standardracks and the racks are loaded via the traywith a capacity of 15 racks = 75 samples.Continuous loading of single racks is alsopossible. Sample and rack identification isdone via an integrated bar-code reader.

Automatic level control in the sampletubes by a liquid level sensor and precisedosing volume ensures sufficient urinesample to be pipetted onto each single

pad of the test strip. In addition, all sam-ples are automatically mixed immediatelybefore the measurement, so that anycomponents which have precipitated aredetected correctly.

The ready-to-use Urisys 2400 Cassettewith 400 test strips allows high conven-ience together with an on-board stabilityof 2 weeks and long calibration interval ofone month.

The high throughput of 240 samples perhour in combination with the large onboard supply of 400 test strips ensuresthat even large numbers of samples canbe processed rapidly. High result memorycapacity allows data storage for 1000 rou-tine samples, 200 STAT samples and 300control samples (100 per control level).Controls are automatically identified viauser definable control racks.

The results of samples or controls can beprinted on an external printer, send to ahost (ASTM standard interface protocol) orcan be stored on a diskette.

Abnormal or edited results are indicated bydifferent flags on the print out.

The limits of the reflectance/concentrationranges can be adjusted to the individualneeds of the user.

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� Integrated bar-code reader for auto-matic sample and rack identification

� User-friendly, intuitive softwareensures easy system operation via color touch screen

� Ports for connection to external printer and Host (ASTM)

� Various setting options for optimaladjustment to the individual operatingsituation and laboratory environment


� Fully automated chemical urinalysis bymeasurement of Urisys 2400 Cassettetest strips

� The innovative, ready to use Urisys 2400 Cassette provides quick and convenient one-grip loadingof cassettes and large on board sup-ply of 400 test strips in a humiditysafe compartment

� High throughput of 240 samples per hour

� Automatic volume control via liquidlevel detection and mixing of samplebefore measurement

73

Detection of microalbuminuria with Micral-Test

urinary albumin. Depending on the albu-min concentration, the detection fieldassumes a color ranging from white tored.

Specificity and sensitivityWith a cut-off at 20 mg/L for microalbu-minuria, the sensitivity is 97% and thespecificity 71%.

On the basis of the immunological reac-tion, Micral-Test measures human albu-min specifically. Cross-reactions with oth-er human proteins such as IgG, IgA,leukocytes, and erythrocytes are below0.5 %.

Test principleMicral-Test allows a specific detection ofhuman albumin in the urine by a combi-nation of chromatographic and immuno-logical processes; human albumin migra-tes from a liquid reservoir into a layer ofconjugate fleece. Here in an immunereaction it is bound specifically to a solu-ble antibody-gold conjugate. The result-ing antigen-antibody complex migratesinto the actual reaction field.

Excess antibody-gold conjugate is boundby immobilized albumin in a capture zone,so that the detection field is reached onlyby conjugate molecules charged with the

75

Detection field

Capture zone

Conjugate fleece

Liquid reservoir

Covering foil withdepth-of-immersion mark

Fig. 26: Structure of Micral-Test strip

5


Test materialThe use of the first morning urine collect-ed in midstream is recommended, be-cause at that time the albumin concentra-tion is not falsified by physical activity orthe intake of fluids. Since albuminuria issubject to physiological variations, themorning urine should preferably be testedon 3 days in a week.

Test performanceNOTE: Since the reaction of this urine teststrip is based on chromatographic andimmunological principles, the procedureis not the same as that with conventionaltest strips.

1. The test strip is dipped for 5 seconds inthe urine sample to a depth such thatthe liquid level is between the twoblack lines. It is then withdrawn. Nei-ther during the dipping nor during thewithdrawal may the strip touch thecontainer wall (possibility of inter-ference effects during chromatography).

2. The test strip is now laid on a non-absorbent horizontal substrate or onthe urine container.

3. After 1 minute the reaction color iscompared against the colors on thelabel. The color predominating over thearea is decisive. Any smaller spots of adifferent color are disregarded in theevaluation.

EvaluationThe result is positive if at least 2 of the 3 morning urine samples give a concen-tration of 20 mg or more albumin per litre.

Sources of errorInterference with the test result may bedue to a number of factors: immersiondepth too large, immersion time too short,reading after an insufficient time, andcontact between the test strip and the wetcontainer wall.

The following findings restrict the inform-ative power of microalbuminuria:� acute diseases and infections of the

urinary tract� positive urine findings for protein,

nitrite, leukocytes, or blood� pregnancy� severe metabolic dysregulation, for

example in diabetics� physical exertion at the time of urine

collection in the bladder (physiologicalalbuminuria)

� albumin of postrenal origin

Influence of drugsInterference due to medicinal drugs hasnot been observed so far, but the effectsof medicines and/or their metabolites onMicral-Test are not all known. In cases ofany doubt, therefore, if this is medicallyacceptable, the medication should be dis-continued and the test carried out onceagain.

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exert an influence on the glomerulopathyand at which the progression towardsrenal failure can still be avoided.

Regrettably, not many doctors takeadvantage of this possibility of improvingtheir therapeutic effectiveness by check-ing their patients for microalbuminuria.

The potential indications include, forexample, metabolic optimization, earlyinstitution of antihypertensive therapy(preferably with ACE inhibitors), and alow-protein diet in the case of diabetics.In hypertensive subjects general meas-ures and an effective drug therapy to low-er the blood pressure are indicated.

Clinical significancePatients with diabetes mellitus or withhypertension often suffer from a nephro-pathy as a late complication. Some30–40% of type I diabetics develop arenal disease after 10–15 years, andrecent studies have shown that ne-phropathies also occur in around 20% oftype II diabetics. In hypertensive patientsthe corresponding figure is around 25%. Ifboth conditions are present simultane-ously, their organ-damaging potential onthe cardiovascular system and on the kid-neys is compounded.

Once an advanced stage with manifestproteinuria, elevated serum urea and cre-atinine, and morphological changes in thekidneys has been reached, the processcan only be slowed down, but no longerarrested, even with good management ofthe underlying disease.

Both diabetic and hypertension-deter-mined nephropathies should therefore bedetected as early as possible, in order tobe able to act on their progressive coursein the direction of terminal kidney failure.

The most important factor in early recog-nition of a nephropathy is microalbumin-uria, defined as albumin concentrationsbetween 20 and 200 mg/L urine. Valuesbelow 20 mg/L are normal. Early diagno-sis of microalbuminuria allows glomerulardamage to be caught at a time at whichappropriate therapeutic measures can still

77


78

+G G

Micral-Test

Antibody-goldconjugate (red)

Albumin(antigen)

Antigen-antibodycomplex

Scheme of the reaction

Free albumin from the urine is bound into an antibody-gold conjugate.An antigen-antibody complex is formed.

+G

Excessantibody-goldconjugate

Flees

Immobilizedalbumin

Immobilizedantigen-antibodycomplex

Scheme of the reaction

Excess conjugate molecules are bound in the capture zoneby immobilized human albumin.

Micral-Test

GScheme of the reaction

The red antibody-gold conjugate charged with albumin from the urine causes a white to redcoloration of the detection field, depending on the albumin concentration in the specimen.

Micral-Test

Fig. 27: Scheme of the reaction in Micral-Test

The Kidneys and the Efferent Urinary Tract

dropwise to the renal pelvis as urine. Theurine then passes into the ureters andthrough them into the bladder. The blad-der is a muscular hollow organ in whichurine is collected. The amount of urinefinally excreted daily through the urethrais approximately 1.5 L.

Function and importance of the urinary organsThe organs of the efferent urinary tractcomprise:� the renal calices� the renal pelvis� ureters� bladder� the urethra

The urinary apparatus is made up of:� two kidneys� two ureters� the urinary bladder� and the urethra

The kidneys are the most importantexcretion organ in the human organism.Every 24 hours around 1500 L of bloodflow through the kidneys, which filter offdaily 170 L of primary urine from thisblood volume. Primary urine is a blood“ultrafiltrate” and consists of water, salt,and dissolved low-molecular blood con-stituents. The water is largely reabsorbed,and all substances needed by the organ-ism are taken up again. The remaining “worthless” substances are conveyed

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Anatomy of the urinary apparatus

Kidney

Bladder

Urethra

AortaInferior vena cava

Ureter

Fig. 28: Anatomy of the urinary apparatus

6


Renal calices/renal pelvisThe renal calices are individual funnel-liketubular structures which open into therenal pelvis, the expansion at the upperend of the ureters.

UretersThe ureters have a length of 24 to 34 cm as measured from the renal pelvis to thepoint at which they enter the bladder. Urine is conveyed down into the bladderby peristaltic contractions of the ureters.

BladderThe bladder is an elastic muscular holloworgan in which the urine is collected.Urine is voided by muscular contractionsof the bladder wall, the abdominal wall,and by the muscle tone of the elastic sys-tem.

UrethraThe urethra is the final excretion channelfor urine. The female urethra is shorterthan the male, and this is the reason why urinary tract infections are morecommon in women than in men.

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� Excretion of blood constituents (e.g. glucose) when their concen-tration exceeds a certain limit.

� Production and degradation of hor-mones (protaglandins) and hormone-like substances which exert an effecton the metabolism and the circulation.

The kidneysThe principal functions of the kidneys areas follows:� Filtration of blood for the purpose of

excretion of toxic products and degra-dation products (metabolic end prod-ucts and toxins, for example urea).

� Regulation of:– the acid-base equilibrium of the

organism– the water and electrolyte balance– the intracellular and extracellular

fluid– blood pressure (secretion of the

hormone renin) and erythropoiesis(secretion of the hormone erythro-poietin)

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Longitudinal section through a kidney

Cortex layer Nephrons (enlarged)Renal cortex

Renal medulla

Pyramids

Renal papillae

Minor calices(calices minores)

Major calix(calix major)

Renal medulla

Renal artery

Renal pelvis

Ureter

Fig. 29: Longitudinal section through a kidney


NephronsThe kidney consists of 1–3 million tubularstructures known as nephrons. Thenephrons can be subdivided further intoglomerular and tubular sections. They areclosely packed and form the renal pa-renchyma (the cortex and the medulla).

Structure of the nephron� renal corpuscle with a glomerulus and

Bowman’s capsule� proximal convoluted tubule� Henle’s loop� the distal convoluted tubule and the

collecting tubule

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The nephron with its glomerularand tubular sections

Collecting tube

Bowman’s capsule

Glomerulus

Renal tubule:Proximal convoluted tubule

Distal convoluted tubule

Henle’s loop

Fig. 30: The nephron with its glomerular and tubular sections


Henle’s loopThe residual filtrate passes into Henle’sloop. Water is removed in the descendingpart by osmosis, and sodium and chlorideare reabsorbed in the ascending part.Excessive reabsorption of water in theascending part is prevented by imperme-ability of the walls to water. This selectivereabsorption process – the countercurrentprinciple – maintains the osmotic gradientof the renal medulla, which is decisive forfinal concentration of the filtrate when itreaches the collecting tubule.

Distal convoluted tubule and the collecting tubuleIn the terminal section of the nephron (thedistal convoluted tubule and the collect-ing tubule) the composition of the urine isfurther modified by continuing reabsorp-tion of sodium and potassium and bysecretion of hydrogen ions. The hormonesadiuretin and aldosterone exert an influ-ence on the water-absorption process,changing the wall permeability (loss orretention of water) and regulating thechemical equilibrium via ion exchange.This equilibrium is the actual end determi-nant for urine volume and urine concen-tration.

Renal corpusclesBlood enters the glomerulus via a bloodvessel and undergoes filtration throughthe membrane (semipermeable basalmembrane) of the glomerular capillariesinto Bowman’s capsule. The renal corpus-cle acts as a “point of contact” betweenthe blood vessel and the place where pri-mary urine is filtered out. The gap be-tween the two walls of Bowman’s capsuleserves as a container for primary urineglomerular filtrate and enables the pas-sage of primary urine through the openend into the proximal tubule.

Proximal convoluted tubulesIn the proximal convoluted tubule all sub-stances that can be utilized by theorganism are actively reabsorbed out ofthe glomerular filtrate and taken up againinto the metabolism, while others areconcentrated and excreted with the urine.The utilizable substances include, forexample, sodium, potassium, amino acids,phosphates, and glucose (glucose shouldnot be present in the urine).

The urine volume is drastically reducedhere – 99% of the primary urine volume isreabsorbed.

The proximal tubule connects the glo-merulus with Henle’s loop.

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Epithelial cells Urine sediment

84

Fig. 1: Group of pavement epithelium cells (×1000). These are the largest cells encountered in urinary sedi-ment (30–50 µm).

Fig. 2: Pavement epithelium cells, transitional epitheli-um cells (urothelial cells) (×450).

Fig. 3: Binuclear transitional epithelium cells (×1000).Urothelial cells measure about 20–30 µm, easily take upwater, and are usually the plumpest structures encoun-tered.

Fig. 4: Group of transitional epithelium cells (×1000).Exfoliation of urothelial cells may be indicative of apathological process in the lower part of the urinarytract.

Fig. 5: Group of suspicious urothelial cells (×1000). Fig. 6: Group of about 15 urothelial cells (×1000). In addition to various signs of malignancy the cellsshow a dysplastic vacuolated cytoplasm.

Urine sediment Tubular epithelium cells

85

Fig. 7: Epithelial cells probably of tubular origin (×1000).Identification of renal epithelial cells is often difficult.

Fig. 8: Three epithelial cells probably of tubular origin(×1000). The characteristic cell clustering and the cylindricalform point to tubular origin.

Fig. 9: Tubular epithelium cells, dysmorphic erythro-cytes, and a leukocyte (×1000). The cylindrical cells have eccentric nuclei and a weaklyexpressed brush border.

Fig. 10: Tubular epithelium cells (×450). The occurrence of tubular epithelium cells in large clus-ters is unusual.

Fig. 11: Degenerating tubular epithelium cells (×1000).Phagocytosis of considerable amounts of urine consti-tuents leads to cell overloading and degeneration. Thenon-functional epithelial cells are then excreted inurine.

Fig. 12: Tubular epithelium cells (“fat granule cells”)(×1000). As a result of excessive lipid storage these cells areclearly larger than other tubular epithelium cells andpoint to a severe renal function disturbance.

Eumorphic erythrocytes Urine sediment

86

Fig. 13: Eumorphic erythrocytes, leukocytes (×1000).Morphologically normal so-called eumorphic subrenalerythrocytes show that a disorder of the efferent urinarytract is present.

Fig. 14: Eumorphic biconcave erythrocytes (×1000).Eumorphic erythrocytes not showing the cell membranealterations typical in erythrocytes of renal origin.

Fig. 15: Eumorphic erythrocytes (×400). Fig. 16: Eumorphic erythrocytes, round epithelial cells(×1000). Juvenile erythrocytes with typical biconcave form; someof the cells show a transition to a crenated form.

Fig. 17: Eumorphic erythrocytes (×1000). Erythrocytes change their form depending on the sur-rounding osmotic pressure gradient. In concentratedhypertonic urine they shrink very quickly and appear ina crenated form.

Fig. 18: Eumorphic erythrocytes (×1000). In alkaline or hypotonic urine erythrocytes swell up andundergo haemolysis. The cell-membrane residues arecalled erythrocyte shadows.

Urine sediment Dysmorphic erythrocytes

87

Fig. 19: Dysmorphic erythrocytes (×1000). Erythrocytes that have undergone morphologicalchanges in the kidneys are designated as “dysmorphic.”

Fig. 21: Various kinds of dysmorphic erythrocytes (×1000). Erythrocytes of glomerular origin can point to the pres-ence of a very wide range of morphological abnormali-ties.

Fig. 22: Dysmorphic erythrocytes (×1000). Erythrocyte shadows of glomerular origin (see Fig. 18,subrenal erythrocyte shadows).

Fig. 23: Dysmorphic erythrocytes (×1000). Erythrocyte shadows of glomerular origin (see Fig. 18,subrenal erythrocyte shadows).

Fig. 24: Dysmorphic erythrocyte (×1000). Blue field: interference contrast microscopy; brownfield: light-field microscopy.

Fig. 20: Dysmorphic erythrocytes (×1000). Morphological abnormalities of the erythrocyte mem-brane are probably attributable to sustained changes inpH and osmolality in the tubule system.

Leukocytes Urine sediment

88

Fig. 25: Neutrophilic polymorphonuclear granulocytes(×1000).These are easily recognizable by their segmented nucleiand, when present in large numbers, point to an inflam-matory disease in the urogenital tract.

Fig. 26: Leukocytes, yeast cells (×400).An opportunistic infection with Candida albicans is a relatively frequent finding.

Fig. 27: Leukocytes, pavement epithelium cells (×1000).In women large numbers of pavement epithelium cellsand granulocytes in the sediment of spontaneous urinemay be due to a vaginal contamination.

Fig. 28: Leukocytes, erythrocytes, bacteria (×1000). Signs of cytolysis are evident in both erythrocytes andleukocytes (alkaline reaction of the urine in bacterialinfections).

Fig. 29: Leukocytes, urothelial cells (×400). Urinary sediment with characteristic signs of an acuteor chronic urinary tract infection.

Fig. 30: Leukocytes, triphosphate, bacteria (×400). Triphosphate crystals are often encountered in infectedalkaline urine, but they can be indicative of obstructedurine flow.

Urine sediment Casts (1)

89

Fig. 32: Small leukocyte cast (×1000). Leukocyte casts are pathognomonic for pyelonephritis.

Fig. 33: Leukocyte cast (×400). A prerequisite for the formation of leukocyte casts isincreased intrarenal excretion of leukocytes in patholo-gical proteinuria.

Fig. 34: Erythrocyte cast (×1000). Erythrocyte casts are pathognomonic for glomeru-lonephritis.

Fig. 35: Erythrocyte cast (×1000). The erythrocytes are partly embedded in a matrix of ahyaline cast and partly attached to a finely granulatedsurface.

Fig. 36: Mixed erythrocyte cast (×1000). Hyaline cast with dysmorphic erythrocytes, tubularepithelium cells, and granular material on the cast sur-face.

Fig. 31: Hyaline cast (×400). Hyaline casts, which can also occur in the urine ofhealthy persons, are often overlooked because of theirlow refractive index.

Casts (2) Urine sediment

90

Fig. 37: Epithelial cast (×400). Epithelial casts occur very rarely in sediment. They con-sist of desquamated tubular epithelium cells bound intothe matrix of a hyaline cast.

Fig. 38: Finely granular cylindrical cast (×400). Granular casts are encountered in nearly all forms ofspecific kidney diseases.

Fig. 39: Coarsely granular cast (×400). Helically twisted cylindrical cast with coarsely granularmaterial (weakly discernible cell structure).

Fig. 40: Granular cast (×400). Extended granular cylinder with many embedded dys-morphic erythrocytes.

Fig. 41: Extended waxy cast (×400). A number of dysmorphic erythrocytes adhere to the“waxy” surface of the cast, which is surrounded by ab-normal sediment structures.

Fig. 42: Waxy cast (×100). Cylindrical waxy casts are always indicative of severechronic kidney diseases (advanced renal failure).

Urine sediment Histiocytes, bacteria, carcinoma cells

91

Fig. 44: Bacteria on a pavement epithelium cell (×1000).Bacteria are often encountered on the surface of largeepithelial cells. If neither inflammation sources norprotein can be found, the bacteria are usually due tocontamination.

Fig. 45: Group of yeast cells (×1000). Free-swimming yeast cells are easily confused with ery-throcytes or fat droplets. Attention should be paid tobranching hyphae and to clumps of budding yeast cells.

Fig. 46: Urothelial carcinoma cells (×1000). In the presence of large groups of urothelial cells thereis always a suspicion of a tumour in the region of theefferent urinary tract.

Fig. 47: Cells of a poorly differentiated bladder carcino-ma (×1000). Characteristic features of malignancy: anisocytosis andnuclear polymorphism, disturbed nucleus/cytoplasmratio, hyperchromatism of the cell nuclei or the cellwalls, multiple nucleoli.

Fig. 48: Group of urothelial carcinoma cells (×1000).Characteristic features of malignancy: complete loss ofcytoplasm in some cells, aniosocytosis and nuclearpolymorphism, thick cell nucleus membrane.

Fig. 43: Histiocyte (× 1000). Histiocytic exhibit substantial variations in size. Theyusually contain numerous vacuoles, granules and otherphagocytic material.

Urine Cytology

92

Normal urothelial cell surrounded by erythrocytes Bladder carcinoma G3, dedifferentiated cells withlarge nuclei, vacuoles, and nucleoli

Bladder carcinoma G2, hyperchromatic nuclei,numerous nucleoli, destructive changes in the cyto-plasm, several leukocytes in the surrounding region

Bladder carcinoma G3, some hyperchromatic nuclei,small cells, multiple nucleoli, hyperchromatism ofthe nucleus walls

Bladder carcinoma G2, distinct variance in nucleussize, multiple nucleoli, nucleus/cytoplasm ratioshifted in favour of the nuclei

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Glossary of Specialist Medical Terms

Acidosis A metabolic disturbance associated with a shift of the acid-base balance to the acid side (pH <7.0)

Adenoma Mostly benign epithelial tumour derived from glandularepithelium

Adiposity Obesity

Agar A polysaccharide obtained from various marine algae andused, among others, for the preparation of nutrient mediafor bacterial cultures

Alimentary Due to nutrition

Alkalosis A metabolic disturbance associated with a shift of the acid-base balance to the alkaline side (pH >7.0)

Alkaptonuria Excretion of homogentisic acid in the urine causing a darkto black discoloration of the specimen in air due to alka-lization

Anaemia “Blood deficiency,” a collective term for diseases based ona reduction in the amount of haemoglobin and usually alsoof erythrocytes in the blood

Anamnesis Complete medical history of the patient (including earlierillnesses and diseases running in the family); the anamne-sis is the first diagnostic step and is of major significance

Anisocytosis Occurrence of erythrocytes of various sizes in blood, afeature of a number of blood diseases

Apoplexy Stroke

Appendicitis Inflammation of the vermiform appendix, a wormlike diver-ticulum of the caecum

Ascorbic acid Vitamin C

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Bacteriuria Excretion of bacteria in urine

Benign Not malignant

Cast Cylindrical protein-containing structure formed withinrenal canaliculi and detected in urinary sediment; casts aredifferentiated according to their constituents

Catalysis Acceleration of a chemical reaction by a material (catalyst)which lowers the activation energy for the process

Cerebral blood flow Circulation disturbance in the braindisturbance

Cholangiolitis Inflammation of the fine terminal elements of the bile ductsystem

Cholangitis Inflammation of the bile duct

Cholestasis Bile congestion in the gallbladder

Cholecystitis Inflammation of the gallbladder

Chyle Milky turbid fluid contained in the intestinal lymph vessels

Chyluria Excretion of chyle in the urine

Cirrhosis Cicatricial shrinkage of an organ

Coagulopathy Blood coagulation (clotting) disturbance due to a plasmafactor deficiency in blood

Colic Acute spasm-like pains in the abdominal region

Congenital Present at and usually before birth

Constipation Infrequent or difficult evacuation of the faeces

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Contamination Soiling, pollution

Cystalgia Pain in the bladder

Cystitis Inflammation of the bladder

Dehydration Withdrawal of water

Diabetes mellitus Chronic metabolic disturbance with delayed or incompleteutilization of glucose in the organism

Diabetic coma Life-threatening disturbance of consciousness due to adiabetic metabolic dysregulation

Dilated Expanded

Discharge Excretion of a fluid from the female sex organs

Diuresis Excretion of urine

Diuretics Drugs promoting urine excretion

Dysmorphic Morphologically altered (malformed)

Dysuria Urine evacuation disturbance

E.(scherichia) coli Gram-negative bacteria in human large intestine; E. colican also provoke urinary tract infections, diarrhoea, sepsis,various inflammations, etc.

Electrophoresis Movement of electrically charged particles in a carriermaterial under the influence of an electric field (used inmedicine for analytical purposes)

Emphysema Accumulation of air in tissues, inflation of organs or bodyparts

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Encephalopathy Brain disease

Endocarditis lenta Bacterial inflammation of the endocardium, the liningmembrane of the heart cavities

Enterocolitis Inflammation of the small and large intestine

Enterohepatic Relating to the intestine and the liver

Enterococci Gram-positive bacteria normally forming part of the intes-tinal flora; outside the intestine they may, however, act aspathogens (e.g. of urogenital infections)

Enuresis Involuntary passage of urine, bed-wetting

Epithelial cells Cells of the topmost tissue layers; urogenital epithelial cellsare a constituent of urinary sediment

Erythrocytes Red blood corpuscles; haemoglobin-containing cells re-sponsible for the transport of oxygen and carbon dioxide inblood

Eumorphic Morphologically unchanged (showing a normal form)

Excretion Elimination of waste metabolic products from the body

Exfoliation Gradual peeling of dead tissue and bone components

Extrarenal Outside the kidneys

Extravasate Fluid such as blood or lymph escaping from a vessel intothe surrounding tissue

Filariasis A disease state caused by the presence of nematodeworms in the body

Glomerulonephritis Renal inflammation affecting mainly the glomeruli

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Glomerulopathy Pathological alteration of the glomeruli

Glomerulus A capillary vessel cluster in the kidneys, site of the firstphase of urine formation

Glucosuria Excretion of glucose in urine

Gonococci Gram-negative bacterial species responsible inter alia forgonorrhoea

Gram-negative Assuming a red color on Gram staining

Gram-positive Assuming a blue color on Gram staining

Gram stain The most important differential-diagnostic stain in bacte-riological examinations

Granulocyte A large white blood corpuscle, the leukocyte species en-countered most frequently in pathological urine

Haematuria Excretion of destroyed (lysed) red blood corpuscles withthe urine

Haemoglobin The pigment of red blood corpuscles

Haemoglobinuria Presence of dissolved haemoglobin in urine as a result oferythrocyte lysis

Haemolysis Destruction of red blood corpuscles by release of haemo-globin

Haemophilia “Blood disease,” a genetically determined blood clottingdisturbance

Haemorrhagic diathesis Abnormal tendency towards bleeding

Heart failure Myocardial weakness, insufficient functional performanceof the heart

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Hepatic Relating to the liver

Hepatitis Inflammation of the liver

Hyperchromatism Increased staining capacity of cell nuclei

Hyperemesis gravidarum Abnormally severe vomiting during pregnancy

Hyperglycaemia Elevated blood glucose level

Hyperosmolar coma Increased osmolarity of the serum due to pronouncedhyperglycaemia in so-called hyperosmolar form of diabeticcoma

Hypertension High blood pressure, a disease of the circulatory systemcharacterized by elevated arterial blood pressure

Hyperuricaemia Uric acid concentration in blood exceeding 6 mg/dL

Hyphae Thread-like fungal cells

Hypoglycaemia Strongly reduced glucose content in blood

Hypotension Chronic low blood pressure

Hypoxia Oxygen deficiency in tissue due to a low oxygen content in blood (reason: respiration impairment or circulation dis-turbance)

Icterus Jaundice, a symptom of various liver diseases and of bileduct obstruction

Ileus Constriction or obstruction of a part of the intestine

Insulin A blood-glucose-lowering hormone formed in the pan-creas

Intermittent Occurring from time to time

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Intoxication Poisoning

Intrahepatic Occurring within the liver

Intracanalicular Situated within an extremely fine tubular passage or chan-nel (canaliculus)

Intrarenal Situated within a kidney

Intravasal Situated within a blood vessel

Ketoacidosis Metabolic disturbance in which there is a shift of the acid-base balance, provoked by increased formation of ketones

Klebsiella A gram-positive bacterial species

Leukocytes White blood corpuscles; a collective term for all nucleus-containing colorless blood cells

Leukocyturia Excretion of leukocytes in urine

Lipogenesis New formation of fats in fat tissue and in the liver

Lipolysis Enzymatic cleavage of fats

Lordosis Physiological curvature of the cervical and lumbar spine

Lupus erythematosus Inflammatory skin disease with bluish-red skin flecks

Lymph The fluid content of the lymph vessels, of major signi-ficance for material exchange in tissues

Lysis Destruction of cells, e.g. erythrocytes or bacteria

Malignant Tending to become progressively worse and resulting indeath

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Metabolite A low-molecular substance formed or transformed in thecourse of metabolic processes

Metaphylaxis Treatment of a patient after recovery from a disease as apreventive measure to avoid possible relapses

Micturition Voiding of urine

Morphology Science of the form and structure of organisms and theirorgans

Mycobacteria Gram-positive bacteria responsible for tuberculosis andleprosy

Necrosis Death of cells, tissues, or organs

Nephritis Inflammation of the kidneys, mostly in the form ofpyelonephritis

Nephropathy General designation for kidney damage

Nucleolus Small strongly staining corpuscle often occurring in largenumbers in cell nuclei

Obstruction Occlusion of cavities and vessels

Orthostasis Upright position of the body

Osmolality Molar concentration of all osmotically active molecules insolution, expressed in weight units

Osmolarity Molar concentration of all osmotically active molecules insolution, expressed in volume units

Osmosis Migration of water molecules through a semi-permeablemembrane separating two solutions of different concen-trations until the concentrations have become equal

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Otitis Ear inflammation

Oxidation Combination of a chemical substance with oxygen

Papillary necrosis Necrosis of renal papillae

Parenchyma Tissue serving for the specific function of an organ (incontrast to connective or supporting tissue)

Parenteral Bypassing the gastrointestinal tract

Pathogenic Provoking disease

Pathognomonic Characteristic of a disease picture

Pathological Caused by a morbid condition

Periarteritis nodosa Rare vascular disease; inflammation of the wall layers ofsmaller arteries with nodule-like outgrowths

Periportal In the neighbourhood of the portal vein

Permeability Penetrability (of a membrane) by fluids

Persistent Continuing to exist, persevering

Phagocytosis Destruction of foreign substances in an organism andmaking them innocuous by “ingesting cells”

Pneumonia Inflammation of the lungs

Pollakiuria Frequent urge to pass water, though only a small amountof urine is voided each time

Polycythaemia Abnormal proliferation of erythrocytes, leukocytes, andplatelets, which leads, among others, to swelling of the liv-er and spleen

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Porphyria A metabolic disturbance with increased excretion ofporphyrins in the urine

Postrenal Occurring functionally downstream of the kidneys

Precipitation Flocculation or settling out in coagulation processes

Predisposition Tendency or sensitivity of the organism to certain diseases

Progressive Increasing, advancing

Prophylaxis Measures serving for the prevention of diseases

Proteinuria Excretion of proteins in urine

Proteus Genus of gram-negative, actively mobile, organisms oc-curring in various distinct forms (putrefaction bacterium,causative agent of urinary tract infections)

Pyelonephritis Simultaneous bacterial inflammation of the renal pelvis andthe kidneys; the most common causative agents are E. coli, Klebsiella, Proteus, and enterococci

Pyuria Excretion of pus in the urine

Reflectance photometry Method of photometric evaluation of urine test strips

Renal Relating to the kidneys

Renal failure Pronounced impairment of kidney function

Renal threshold Maximum reabsorption capacity of the kidneys

Resorption Uptake of food constituents after their digestion throughthe intestinal mucosa, especially in the small intestine

Respiratory Referring to breathing (respiration)

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Retention Physiological: holding of a substance in the organism e.g.as a result of increased tubular reabsorption in the kidneys

Relapse Recurrence (of a past illness)

Rupture Traumatic or spontaneous tearing or disruption of organs

Screening (test) Investigation of large groups of the population for thepurpose of early detection of probable carriers of the tar-get condition; in screening no diagnosis is established, andpositive test results must be followed by further differentialdiagnostics

Semi-permeable Semi-penetrable

Sepsis Blood poisoning

Sinusitis Acute or chronic inflammation of paranasal sinuses

Stricture Narrowing of a body organ by scarring

Suppository Medicated mass intended for introduction into the rectal,vaginal, or urethral orifice

Test-strip screening Stepwise screening method in urine diagnostics in whichonly the urine samples with relevant positive test stripresults are investigated further microscopically or bacteri-ologically

Thrombo(cyto)penia Blood-platelet deficiency

Tonsillitis Inflammation of tonsils

Transient Temporary

Traumatic 1. Producing a wound2. Produced by a lesion3. Leading to psychological shock

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Uraemia Urine intoxication (presence of urea in blood) as a terminalstage of renal failure; the only effective methods of treat-ment are dialysis and kidney transplant

Urethritis Inflammation of the urethra

Urine cytology Evaluation of the cell alterations in a stained smear of urinesediment

Urine status Result of examinations carried out on freshly voided mid-stream urine with multitest strips

Urobilinogenuria Excretion of urobilinogen in the urine

Urolithiasis Formation of urinary stones (calculi) and the resultingpathological condition

Vacuole Hollow cavity in cell nucleus or cytoplasm, filled with awatery or thick-flowing substance

Vasoconstrictive Vessel-narrowing

Further Reading

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Klinke R., Silbernagel S. (eds.)Lehrbuch der PhysiologieStuttgart, Georg Thieme Verlag,2nd ed. 1996

Kouri T., Fogazzi G., Gant V., Hallan-der H., Hofmann W., Guder W.G.European Urinalysis GuidelinesScan J Clin Lab Invest, Vol. 60, Supple-ment 231, 2000

Kutter D.Schnelltests in der klinischen DiagnostikMünchen, Urban & Schwarzenberg, 2nd ed. 1983

Töpfer G., Trefz G., Zawta B.Proteins – Questions and Answers forMedical DiagnosticsCompany brochure of Roche, 2000 – Id. No. 11840380

Voswinckel P.Der schwarze UrinBerlin, Blackwell Wissenschaft, 1992

Zimmermann-Spinnler M.UrinlaborLiestal CH, Medical Laboratory Consulting, 1991

Anders H.J., Schlöndorff D.Mikroskopische Differenzialdiagnostikdes HarnsCompany brochure of Roche, 2002 – Id. No. 03500152

Colombo J.P.Klinisch-chemische UrindiagnostikRotkreuz CH,Labolife-Verlagsgesellschaft, 1994

Guder W.G., Zawta B., Forstmeyer H.(eds.)Important Facts about Diagnostic Testsof Renal Function – Questions andAnswersCompany brochure of Roche,2nd ed. 1999 – Id. No. 12254891

Guder W.G., Zawta B.Fundamentals in Laboratory Medicine –Renal DiseasesCompany brochure of Roche, 2000 – Id. No. 11673670

Hagemann P., Kimling H., Zawta B.Fundamentals of Laboratory Testing –UrineCompany brochure of Roche, 2003 – Id. No. 12117932

urine strips

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