Imaging and technology in urology
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This document discusses urinalysis using dipstick tests. It provides details on the components typically included on dipstick strips, how to perform the test, and the significance of each component. Key components include bilirubin, glucose, haemoglobin, ketones, leucocytes, nitrites, pH, protein, specific gravity, and urobilinogen. The document outlines how each component is detected, its sensitivity and specificity, potential significance in detecting diseases like urinary tract infections or renal disease, and possible sources of errors in the dipstick tests.
Imaging and technology in urology
- 1. 127S. Payne et al. (eds.), Imaging and Technology in Urology, DOI 10.1007/978-1-4471-2422-1_28, © Springer-Verlag London 2012 Urinalysis is a quick, cheap, and readily available point of care test. The combina- tion of reagents present on dipstick strips typically include: (1) bilirubin, (2) glu- cose, (3) haemoglobin, (4) ketones, (5) leucocytes, (6) nitrites, (7) pH, (8) protein, (9) specific gravity, and (10) urobilinogen. Using a Dipstick Dipstick tests vary between manufacturers, so users should familiarise themselves with the product used in their department. To avoid degradation, dipsticks must be stored in a closed container; a useful check for such changes is a positive glucose strip pre-testing. Always check the expiry date. The urine sample should be mid- stream, fresh and collected in a sterile container. Submerge all the pads of the strip in the sample and remove immediately. Start timing. Read each test at the appropriate time by comparing against the colour reference chart on the bottle. Urinalysis: Chemistry, Significance, and Errors Blood/Haemoglobin How? – Dependent on the peroxidase-like activity of haemoglobin (or myoglobin). This catalyses the oxidation of a chromagen (3,3¢,5,5¢-tetramethylbenzidine) by an organic peroxide (e.g., diisopropylbenzene dihydroperoxide). It can detect free D.G. Ross, MD, FRCS (Urol.) Department of Urology, Salford Royal NHS Foundation Trust, Stott Lane, Salford, M6 8HD, UK e-mail: david.ross@srft.nhs.uk Chapter 28 Urinalysis David G. Ross
- 2. 128 D.G. Ross haemoglobin and intact erythrocytes which lyse on the test pad. Free haemoglobin gives a uniform colour change (orange, green, blue), while intact red blood cells give a spotted appearance; green spots on yellow/orange background. Sensitivity=90% in detecting equivalent of >3 RBCs/hpf; specificity=65–80%. A trace of haematuria should be considered negative, while ³1+ is considered significant. Non-haemolysed and haemolysed are of equal significance. Who to Investigate – BAUS Haematuria Guidelines: 1. Single episode of symptomatic nonvisible haematuria (in the absence of UTI or other transient cause) 2. Persistent (two out of three dipsticks positive) asymptomatic non-visible haema- turia in patients ³40 years Significance – 5% of patients will have urological cancer (Table 28.1). Protein How? – Based on protein error of indicators principle. Tetrabromophenol blue changes colour in response to the presence of protein in urine. Sticks are very sensi- tive, and a trace corresponds to 0.15–0.3 g/L, + to 0.3 g/L, ++ to >1 g/L, +++ to 2.5–5 g/L, and ++++ to >10 g/L proteinuria. Normal urinary protein should be less than 15 mg/dL or <150 mg/24 h. Significance – Significant proteinuria is a risk factor for renal disease and cardio- vascular morbidity and mortality. Patients with persistent proteinuria should have it quantified using either albumin/creatinine or protein/creatinine ratio. ACR has bet- ter sensitivity than PCR for low levels of proteinuria. Even microalbuminuria (30– 150 mg/24 h) is significant in diabetic patients. In the context of the definitions of chronic kidney disease, CKD 1=GFR ³90 mL/min and proteinuria, and CKD 2=GFR 60–89 mL/min and proteinuria. Both groups require monitoring in primary care. A nephrology referral is indicated if the urinary ACR>70/PCR>100 mg/mmol or the urinary ACR>30/PCR>50 mg/mmol with microscopic haematuria. Table 28.1 Diagnoses of patients investigated for microscopic haematuria (Khadra et al. 2000) Diagnosis % of patients No cause identified 68.2 UTI 13 Nephrological causes (IgA nephropathy, etc.) 9.4 Bladder cancer 4.8 Stones 4 Prostate cancer 0.3 Kidney cancer 0.2 Upper tract urothelial cancer 0.1
- 3. 12928 Urinalysis Leucocytes How? – Leucocyte esterase is produced by neutrophils which catalyses the hydro- lysis of either derivatised pyrrole amino acid ester to liberate 3-hydroxy-5-phenol pyrrole or indoxyl carbonic acid ester to indoxyl. Pyrrole or indoxyl then reacts with a diazonium salt to produce a purple product. Significance – The list of potential causes of persistent pyuria is long; however, the presence of urinary leucocytes is often used as an indicator of UTI along with dipstick nitrites. Its performance in this setting is shown in Table 28.2. Nitrites How? – Nitrite in the urine reacts with r-arsanilic acid to form a diazonium com- pound which couples with 1,2,3,4-tetrahydrobenzo(h)-quinolin-3-ol to produce a pink colour. Significance – Nitrites when present in urine are the result of bacteria reducing urinary nitrates. Around 60% of Gram-negative bacteria are capable of this, which, together with the requirement of at least 105 bacteria per milliliter for a positive test, limits the sensitivity of this test in the clinical detection of UTI (Table 28.2). pH How? – Double indicator principle, methyl red and bromothymol blue, which pro- vides a broad range of colours to cover a urinary pH range of 5–8.5 (visually). Significance – Urinary pH typically reflects plasma pH. An exception is in renal tubular acidosis where there is an inability to acidify urine in response to an acid load. Urinary pH is potentially important in urolithiasis. Uric acid stone formation requires a pH < 5.5, while the actions of urease-splitting organisms provide the alkaline environment for struvite lithogenesis. Dietary factors can alter pH; high protein diets lower pH, while citrate supplements will raise it. Table 28.2 Utility of leucocyte esterase and nitrite urinalysis in the detection of UTI (St John et al. 2006) Dipstick result Pooled sensitivity % Pooled specificity % LE positive 72 82 Nitrite positive 54 98 LE or nitrite positive 81 77 LE and nitrite positive 43 96
- 4. 130 D.G. Ross Glycosuria How? – Double sequential enzyme reaction: 1. Glucose oxidase catalyses glucose→glyconic acid+hydrogen peroxide. 2. Peroxidasecatalyseshydrogenperoxide+potassiumiodidechromagen→coloured oxidised chromagen. Significance – Occurs when blood sugar is >10 mmol/l, the renal threshold. Potential Errors When Reading a Dipstick Potential sources of false positive and negative dipstick test results are shown in Table 28.3. References Khadra MH, et al. A prospective analysis of 1,930 patients with hematuria to evaluate current diagnostic practice. J Urol. 2000;163(2):524–7. St John A, et al. The use of urinary dipstick tests to exclude urinary tract infection: a systematic review of the literature. Am J Clin Pathol. 2006;126(3):428–36. Table 28.3 Sources of false positive and negative urine dipstick results Test False positive False negative Haemoglobin Myoglobin Reducing agents: Bacterial peroxidases 1. Ascorbic acid Hypochlorite 2. Captopril Menstruation Dehydration Exercise Protein – Dilute or alkaline urines Bence-Jones proteins Leucocytes Formalin Glycosuria (>3 g/dL) Vaginal discharge Ascorbic acid Cephalexin Imipenem Meropenem Clavulanic acid Tetracycline Nitrites – Non-nitrate-reducing bacteria Low nitrate diets Dilute urine Urine in the bladder for <4 h Ascorbic acid Glucose – Ascorbic acid