Stefan G Kiessling MD FAAP Stefan G Kiessling, MD, FAAP To briefly - - PowerPoint PPT Presentation

Stefan G Kiessling MD FAAP Stefan G Kiessling, MD, FAAP

 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 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

• f urinalysis and microscopy

 Easy inexpensive tool to diagnose illnesses that could

• therwise remain undiagnosed and to follow therapy

response to certain diseases

 Diabetes mellitus

Diabetes mellitus

 Glomerulonephritis  Hypertension related renal injury  Non‐symptomatic UTIs  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

 In the office setting, clean catch midstream voided

specimen are collected most commonly specimen are collected most commonly

 Make sure to label properly with name, MR#, DOB to avoid

mix up with sample from another patient S i h ld b i d ithi i t t h

 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

f i t refrigerator

 Urine sediment should be reviewed in certain cases:

 Spin 5‐10 ml of urine at 2500‐3000r/min for 3‐5 minutes  Discard the supernatant and resuspend sediment in remaining  Discard the supernatant and resuspend sediment in remaining

amount of urine

 Transfer one drop of urine to a slide and coverglass

Analysis Of The Urine Sediment Analysis Of The Urine Sediment y

► Take minimum of 8

Take minimum of 8‐10 cc of urine (if available); spin at 10 cc of urine (if available); spin at 2000 2000‐3000 3000 RPM for 3 RPM for 3‐5 minutes with 5 minutes with > 5 RBC/HPF 5 RBC/HPF RPM for 3 RPM for 3 5 minutes with 5 minutes with > 5 RBC/HPF 5 RBC/HPF

► Discard supernatant and

Discard supernatant and resuspend resuspend pellet in remaining urine pellet in remaining urine

► Put the cover glass on in

Put the cover glass on in an an angle so that possible casts get washed to angle so that possible casts get washed to the opposite side the opposite side the opposite side the opposite side

Casts

► If there is microscopic hematuria on an initial clean catch urine,

If there is microscopic hematuria on an initial clean catch urine, repeat at least one more repeat at least one more time 2 time 2‐3weeks later 3weeks later since high (>50 since high (>50‐70) “false 70) “false positive” rate (Dodge et al., 1976) positive” rate (Dodge et al., 1976)

 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) :

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  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

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

 Yellow: normal  Amber to reddish brown:

 RBC – hemoglobin – myoglobin – hemosiderin

 Bright red:

Bright red:

 Fresh blood, urates (infant diapers), porphyrins, pyridium,

adriamycin, food coloring, beets  Brown‐Black:

Brown Black:

 Alkaptonuria, melanin, methyldopa

 Bright orange:

 Rifampin  Rifampin

 Dark orange:

 Bilirubin, carotin

Brewer E.

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

E t d D tibi ti

 Excreted Drugs: antibiotics

 Should be read as soon as dipstick is taken out of urine specimen

 Alk li H d t l f l til ( i f t  Alkaline pH due to loss of volatile gases (conversion of urea to ammonia in the presence of bacteria and loss of CO2)

 Range quite wide from 4.5 to 7 in normal individuals but usually

id ( 6) d t b idi i d f ti f d il 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

 Range seen usually is between 1.003 and 1.035  Reflects number and size of particles in solution  Expected value: L i l l di d hi h i l d fi i b h fl i

 Low in volume loading and high in volume deficit both reflecting

appropriate tubular function  Unexpected value:

 Low SG in ARF or oliguria reflecting tubular dysfunction

 Normally not seen unless serum glucose passes renal

threshold (>180mg/dl)

 Dipstick is specific for glucose (need other testing for

galactose fructose lactose) galactose, fructose, lactose)

 Not a good indicator for diabetes control  Glucose in the urine does not always reflect hyperglycemia

G y yp g y but can be a sign of abnormal tubular reabsorption (need concomitant serum glucose to rule out renal glucosuria) F l i i i h f b i Vi i C d

 False positive in the presence of bacteria, Vitamin C and

ASA (acetylsalicylic acid)

 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 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  0: 0 mg/dl  Trace: 1‐10 mg/dl  1+: 15‐30 mg/dl  2+: 40‐100 mg/dl  3+: 150‐350 mg/dl  4+: >500 mg/dl

 < 1 g per day

 Transient – postural – tubular – glomerular

Transient postural tubular glomerular  > 3 g per day

 Glomerular

 False positive results

 Macroscopic hematuria  Pyridium (phenazopyridine)

y (p py )

 Urine pH >8  Vaginal secretions  chlorhexidine

chlorhexidine

 Normal < 3 RBC per high power field (HPF)  Results are trace to 3+  Results are trace to 3+  Positive dipstick does not exclude pigmenturia 

true hematuria needs to be confirmed by RBCs on t ue e atu a eeds to be co ed by R Cs o 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 RBC morphology can help to determine glomerular

• vs. non‐glomerular hematuria

 False positives:

 Betadine, hypochlorite cleansers (oxidize dip‐stick reagent)  Other chemicals  Positive dipstick without RBCs ‐> dilute urine (SG<1.006) leading to

p ( ) g red cell lysis

 Excess bacterial peroxidase in urine, bacterial overgrowth  Menstruating female

g

 Take home message: A positive dipstick for blood should always

be followed by the assessment for presence or absence of red blood be followed by the assessment for presence or absence of red blood cells

 Product of fat metabolism (largely β hydroxybutyric acid but  Product of fat metabolism (largely β‐hydroxybutyric acid but

also acetoacetic acid and acetone)

 Dipstick only detects acetoacetic acid and acetone thus

p y underestimating true ketone excretion

 Positive in DKA, starvation, anorexia, dieting, vomiting

d

 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

 Reported as 1+ to 3+  Reported as 1+ to 3+  May indicate abnormal liver function tests or biliary

• bstruction

 Is quite unstable and should be read in a timely fashion to

avoid false negative reading l f l f

 Also false negative in presence of Vitamin C

 Degradation product from bilirubin formed by intestinal  Degradation product from bilirubin formed by intestinal

bacteria

 Trace amounts are considered normal since <5% of

bili i t d i th i ( / h ) urobilinogen is excreted in the urine (1‐4mg/24hr)

 Presence can indicate hemolysis, intestinal obstruction or

abnormal LFTs but not biliary obstruction y

 If dipstick is positive for bilirubin but negative for

urobilinogen, think about biliary obstruction (absence of bilirubin in the intestine, no bacterial metabolism) bilirubin in the intestine, no bacterial metabolism)

 Dietary nitrate is normally excreted in the urine  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 q ) y g g reduce nitrate to nitrite

 False negative results in the presence of Vitamin C, yeast or

iti b t i d i t i (l it t gram positive bacteria and in vegetarians (low nitrate production)

 Essentially confirms presence of polymorph nuclear cells  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  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

 PKD

 Red blood cells  Red blood cells  White blood cells  Renal tubular epithelial cells  Transitional epithelial cells  Squamous epithelial cells

C t l

 Crystals  Casts  Bacteria  Artifacts (Fiber, starch crystals, air bubbles)  Mucous threads (normal in low quantity, high quantity in

i f ti /i it ti f th i t t) infammation/irritation of the urinary tract)

 Small smooth no nucleus  Small, smooth, no nucleus  Normal <3 RBC per HPF  They lyse in dilute, alkaline and non‐fresh urine samples

They lyse in dilute, alkaline and non fresh urine samples

 Dysmorphic RBCs ‐ acanthocytes

 Spherical larger than RBCs dull gray characteristic granules  Spherical, larger than RBCs, dull gray, characteristic granules

and lobulation of the nucleus (0‐4/HPF)

 Normal urine contains up to 2000 leukocytes/ml

p y

 Slighly larger than WBCs with a large round nucleus that

can be eccentric

 Cuboidal, Columnar or teardrop shaped

S i ATN d t h t i

 Seen in ATN and exposure to nephrotoxins  Oval fat bodies: tubular cells with lipid particles (seen

• ften in urine sediment in nephrotic syndrome)

p y )

 Normal urine component  If present in large quantities  need to think about

neoplasm

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

 In acidic urine

 Calcium oxalate – normal after intake of oxalate‐rich foods

(spinach, tomatoes, oranges, asparagus, garlic, rhubarb) – Calcium

• xalate 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 with urease producing orgamism

 Calcium phosphate  Amorphous Phosphate: phosphate salts

Calcium Oxalate Calcium Oxalate

 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

 Usually formed by precipitation of Tamm‐Horsfall

mucoprotein (which is secreted by the tubules) and the 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  Thin or broad (often correlating with duration of

underlying disease)

 Hyaline casts:

 found in very concentrated urine  found in very concentrated urine  Exercise or stress induced  Proteinuria

 Cellular casts:

Cellular casts:

 RBC casts: Glomerulonephritis and vasculitis  WBC casts: pyelonephritis and tubulointerstitial disease  Tubular casts: ATN or other renal tubular damage

 Granular casts:

 Coarse or fine  Degenerating cellular casts  Aggregated protein

gg g p  Fatty casts:

 Heavy proteinuria as in nephrotic syndrome

W

 Waxy:

 Advance renal failure

Red blood cell cast White blood cell cast

 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 the time represent contamination

Glomerular Glomerular Tubular Tubular Interstitial Interstitial Vascular Vascular Heme positive Heme positive + + + + + + + + + +

• /+

/+ + + + + Protein 2+ Protein 2+ + + + + + +

• /+ +

/+ +

• /+

/+ Protein 2+ Protein 2+ + + + + + + /+ + /+ + /+ /+ Dysmorphic Dysmorphic RBC RBC + + + + + +

• /+

/+ + + + + Renal cells Renal cells 15 15-

• 20

20

• /+

/+ + + + + + + + + + + RBC casts RBC casts + + + +

• +

+ Granular casts Granular casts + + + + + + + + + + Heme/granular Heme/granular + + + + + + + + + + + + + Heme/granular Heme/granular casts casts +

• + + +

+ + + + + + + + +

Herrin, JT.