To briefly review the anatomy and physiology of the urinary system To review the basics of urinalysis and urine sediment in

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1 Stefan G Kiessling, MD, FAAP

2 To briefly review the anatomy and physiology of the urinary system To review the basics of urinalysis and urine sediment in children pertinent to a primary care provider s needs To review normal and abnormal findings of the urinalysis and urine sediment and correlation with clinical pathology To discuss a further diagnostic approach based on findings of urinalysis and microscopy

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5 Easy inexpensive tool to diagnose illnesses that could otherwise remain undiagnosed and to follow therapy response to certain diseases Diabetes mellitus Glomerulonephritis Hypertension related renal injury Non symptomatic UTIs AAP News 2010(12):31 UA should only be done in children at risk or with certain medical conditions but NOT used as a routine tool

6 In the office setting, clean catch midstream voided specimen are collected most commonly Make sure to label properly with name, MR#, DOB to avoid mix up with sample from another patient Specimen should be examined within 30 minutes to 1 hour after voiding either in the office or set to the lab Collect new sample if >1 hr at room temperature or >4 hr in refrigerator fi Urine sediment should be reviewed in certain cases: Spin 5 10 ml of urine at r/min for 3 5 minutes Discard the supernatant and resuspend sediment in remaining amount of urine Transfer one drop of urine to a slide and coverglass

7 Analysis Of The Urine Sediment Take minimum of 8 10 cc of urine (if available); spin at RPM for 3 5 minutes with > 5 RBC/HPF Discard supernatant and resuspend pellet in remaining urine Put the cover glass on in an angle so that possible casts get washed to the opposite side Casts If there is microscopic hematuria on an initial clean catch urine, repeat at least one more time 2 3weeks later since high (>50 70) false positive rate (Dodge et al., 1976)

8 Remember: In adolescent and obese females, the labia must be spread apart to get a proper clean sample MOST girls don t do that Eileen Brewer (Peds Nephrologist at Baylor) : Her husband urologist says that if your hands are not wet after you collect the sample, you did not do it right Do not squeeze the diaper in infants except if you look for protein Uncircumcised male with difficult to retract foreskin: Best method of collection is suprapubic tap Consider In/Out cath

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10 Clear Cloudy Color (red/brown/yellow) Smell

11 Yellow: normal Amber to reddish brown: RBC hemoglobin myoglobin hemosiderin Bright red: Fresh blood, urates (infant diapers), porphyrins, pyridium, adriamycin, food coloring, beets Brown Black: Black: Alkaptonuria, melanin, methyldopa Bright orange: Rifampin Dark orange: Bilirubin, carotin Brewer E.

12 Ammonia: bacteria Fruity: ketones (DM, starvation) Maple Syrup: maple syrup disease Musty: PKU Ingested foods: asparagus Excreted Drugs: antibiotics

13 Should be read as soon as dipstick is taken out of urine specimen Alkaline li ph due to loss of volatile ltil gases (conversion of urea to ammonia in the presence of bacteria and loss of CO 2 ) Range quite wide from 4.5 to 7 in normal individuals but usually acid (5 6); needs to be acidic given need for excretion of daily acid load of 2mEQ/kg/day Usually of little importance ph>7.5 in vegetarian (vegan) diet or urease producing organisms (Proteus; nitrite usually also positive) Urine ph below 5.3 in the setting of metabolic acidosis, if not, think about RTA Excess urine runover from protein reagent can falsely lower urine ph

14 Range seen usually is between and Reflects number and size of particles in solution Expected value: Low in volume loading and high h in volume deficit fii both reflecting appropriate tubular function Unexpected value: Low SG in ARF or oliguria reflecting tubular dysfunction

15 Normally not seen unless serum glucose passes renal threshold (>180mg/dl) Dipstick is specific for glucose (need other testing for galactose, fructose, lactose) Not a good indicator for diabetes control Glucose in the urine does not always reflect hyperglycemia y but can be a sign of abnormal tubular reabsorption (need concomitant serum glucose to rule out renal glucosuria) Fl ii i h f b i Vi i C d False positive in the presence of bacteria, Vitamin C and ASA (acetylsalicylic acid)

16 Normal in children as a rule of thumb is <100mg/day Normal small amounts are either filtered by the glomerulus albumin or secreted by the tubule Tamm Horsfall Dipstick tests ONLY for albumin Urine albumin concentration influenced by rate of protein excretion and urine volume In case of concerns of non glomerular proteinuria, need to consider special testing (Beta2 microglobulin, sulfosalicylic acid precipitation) Dipstick: 0: 0 mg/dl Trace: 1 10 mg/dl 1+: mg/dl 2+: mg/dl 3+: mg/dl 4+: >500 mg/dl

17 < 1 g per day Transient postural tubular glomerular > 3 g per day Glomerular False positive results Macroscopic hematuria Pyridium (phenazopyridine) py Urine ph >8 Vaginal secretions chlorhexidine

18 Normal < 3 RBC per high power field (HPF) Results are trace to 3+ Positive dipstick does not exclude pigmenturia true tuehematuria aneeds to be confirmed by RBCs Cson urine microscopy Can spin urine down if supernatant clear hematuria Can originate from anywhere in the urinary tract RBC morphology can help to determine glomerular vs. non glomerular hematuria

19 False positives: Betadine, hypochlorite cleansers (oxidize dip stick reagent) Other chemicals Positive dipstick without RBCs > dilute urine (SG<1.006) leading to red cell lysis Excess bacterial peroxidase in urine, bacterial overgrowth Menstruating female Take home message: A positive dipstick for blood should always be followed by the assessment for presence or absence of red blood cells

20 Product of fat metabolism (largely β hydroxybutyric acid but also acetoacetic acid and acetone) Dipstick only detects acetoacetic acid and acetone thus underestimating true ketone excretion Positive in DKA, starvation, anorexia, dieting, vomiting Reported as trace to 4+ Caveat: false negative in delayed reading of the urine sample false negative in delayed reading of the urine sample False positive in highly pigmented urine, mesna and levodopa metabolites

21 Reported as 1+ to 3+ May indicate abnormal liver function tests or biliary obstruction Is quite unstable and should be read in a timely fashion to avoid false negative reading Also fl false negative in presence of Vitamin C

22 Degradation product from bilirubin formed by intestinal bacteria Trace amounts are considered normal since <5% of urobilinogen is excreted td in the urine (1 4mg/24hr) Presence can indicate hemolysis, intestinal obstruction or abnormal LFTs but not biliary obstruction If dipstick is positive for bilirubin but negative for urobilinogen, think about biliary obstruction (absence of bilirubin in the intestine, no bacterial metabolism)

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24 Dietary nitrate is normally excreted in the urine Useful as a screen for presence of bacteria (if there is adequate contact time), usually gram negative rods which reduce nitrate to nitrite False negative results in the presence of Vitamin C, yeast or gram positive bacteria and in vegetarians (low nitrate t production)

25 Essentially confirms presence of polymorph nuclear cells (PMN) False positive with eosinophilia and trichomonas False negative with Vitamin C and large amounts of albumin Sensitive for UTI but need to think about others in the differential diagnosis: Resolving UTI Glomerulonephritis Renal stone Tubulo interstitial nephritis TB (Interstitial cystitis) PKD

26 Red blood cells White blood cells Renal tubular epithelial cells Transitional epithelial cells Squamous epithelial cells Crystals Casts Bacteria Artifacts (Fiber, starch crystals, air bubbles) Mucous threads (normal in low quantity, high quantity in infammation/irritation it of the urinary tract) t)

27 Small, smooth, no nucleus Normal <3 RBC per HPF They lyse in dilute, alkaline and non fresh urine samples Dysmorphic RBCs acanthocytes

28 Spherical, larger than RBCs, dull gray, characteristic granules and lobulation of the nucleus (0 4/HPF) Normal urine contains up to 2000 leukocytes/ml

29 Slighly larger than WBCs with a large round nucleus that can be eccentric Cuboidal, Columnar or teardrop shaped Seen in ATN and exposure to nephrotoxins Oval fat bodies: tubular cells with lipid particles (seen often in urine sediment in nephrotic syndrome)

30 Normal urine component If present in large quantities need to think about neoplasm

31 Usually less than one if the urine is a clean catch Larger numbers indicate vaginal contamination

32 In acidic urine Calcium oxalate normal after intake of oxalate rich foods (spinach, tomatoes, oranges, asparagus, garlic, rhubarb) Calcium oxalate calculi, ethylene glycol intoxication, large amounts od Vit C Uric acid normal or associated with gout, febrile illness, Lesch Nyhan syndrome, tumor lysis syndrome Cystine Cystinuria or cystinosis In alkaline urine Ammonium Magnesium Phosphates (Struvite) coffin lid; UTI with urease producing orgamism Calcium phosphate Amorphous Phosphate: phosphate salts

33 Calcium Oxalate

34 Often seen after urine is refrigerated Of little clinical value Can mimic brownish casts of ATN Occur in acid ph and can be dissolved by adding an alkali like 2% ammonia solution

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36 Usually formed by precipitation of Tamm Horsfall mucoprotein (which is secreted by the tubules) and the clumping of cells or other materials within the protein matrix; they reflect renoparenchymal injury Thin or broad (often correlating with duration of underlying disease) Hyaline casts: found in very concentrated urine Exercise or stress induced Proteinuria Cellular casts: RBC casts: Glomerulonephritis and vasculitis WBC casts: pyelonephritis and tubulointerstitial disease Tubular casts: ATN or other renal tubular damage

37 Granular casts: Coarse or fine Degenerating cellular casts Aggregated g protein Fatty casts: Heavy proteinuria as in nephrotic syndrome Waxy: Advance renal failure

38 Red blood cell cast White blood cell cast

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40 Only few bacteria in UNSPUN urine are essentially diagnostic of a UTI Bacteria in a SPUN urine are NOT diagnostic and most of the time represent contamination

41 Glomerular Tubular Interstitial Vascular Heme positive /+ ++ Protein /++ -/+ Dysmorphic RBC Renal cells /+ ++ -/ RBC casts Granular casts Heme/granular casts Herrin, JT.

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