Urinalysis + Kidney Function Tests Flashcards
Physical examination of urine
- colour
- clarity
- volume
- smell
colour of urine
- major pigment = urochrome, urobilin, uroerythrin
- intensity depends on concentration
- normal: straw light yellow
clarity of urine
- normal: clear, transparent
- turbidity: may result from non-pathological or pathological causes
inability to produce urine
anuresis
fatal urine condition if not managed immediately!
anuria
urine smell
- normal: characteristic faint odour due to volatile acids
- improper storage = bacterial growth
- non-pathological causes = foods, intravenous meds
- pathological disorders = UTI (ammonia), ketone production (fruity odour), amino acid disorders
waxy casts
- end product of cast evolution
- harder to process
- tubular obstruction with prolonged stasis
> chronic renal disease
> renal failure - diseased, dilated tubules (“broad” casts)
urine pH
- normal = 4.5 to 8.0; average is 5.0 to 6.0
- pH should support findings of other lab tests
- acid urine:
> inhibits UTI
> prevents formation of alkaline renal stones (calcium carbonate, calcium phosphate) - alkaline urine:
> high pH may identify improper collection/ storage!!!
> prevents precipitation ad promotes excretion of drugs
> prevent formation of acidic renal stone (calcium oxalate, uric acid, cysteine)
urinalysis: microscopic examination
- prepare urine sediment on a fresh std vol of sample; 450 x g for 5 min; low speed centrifugation avoids disruption of fragile elements
- examine sediment on slide at low power
> use high power to differentiate
> report an average of two low power fields - observe: cells, casts, organisms, crystals
what cells should NOT be present in urine?
- RBCs
- WBCs
- renal tubule cells should not be many!
renal casts
- cylindrical bodies formed in lumen of renal tubules; ‘casts’ of tubule shape
- uromodulin (Tamm-Horsfall mucoprotein): secreted by renal tubule cells; denatures/precipitates at high salt, low pH, low urine flow
- normal = 0-2 hyaline (mucoprotein) casts/low power field
- pathological = RBC casts, WBC casts, waxy
most common renal casts
hyaline cast
granular cast
hyaline cast
- in normal individuals
> dehydration
> vigorous exercise
> stress, fever - increase = renal disease, congestive heart failure
granular cast
- breakdown of trapped cellular elements, aggregated proteins
> after strenuous exercise - increase = chronic renal tubule disease; acute tubular necrosis
RBC casts
- renal disease
- glomerulonephritis
- tubule damage
- nephrotic syndrome (massive protein loss in urine)
WBC casts
- inflammation or infection
- pyelonephritis (inflammation of kidneys)
waxy casts
- end product of cast evolution
- tubular obstruction with prolonged stasis: chronic renal disease, renal failure
- diseased, dilated tubules (“broad” casts)
acid urine
- normal: uric acid, calcium oxalate
- pathological: bilirubin, drugs (sulfonamide, ampicillin); amino acids (cysteine, tyrosine, leucine)
alkaline urine
- normal: amorphous phosphates, triple phosphates (struvite), calcium phosphate, calcium carbonate
- pathological: important if urine sample is fresh; triple phosphates; UTI, calculi (renal stones)
urine pH
- normal pH 4.5-8.0
- acid urine = inhibits development of UTI; prevents formation of alkaline renal stones (Ca carbonate or Ca phosphate)
- alkaline urine = high pH may identify improper collection/storage
> prevents precipitation and promotes excretion of drugs
> prevent formation of acidic renal stone (Ca oxalate, uric acid, cysteine)
T or F. urine pH should support findings of other lab tests
T!
measure of urine concentration based on its density; affected by # of solutes and their MW
urine specific gravity
1.002 -1.040
2 methods of measuring urine specific gravity
- polyelectrode pH indicator (~ionic strength)
- refractive index
urine glucose
- normally absent
- glucosuria = DM
- detected by glucose oxidase method (linked to peroxidase rxn)
- other sugars may appear in urine = not detected
urine ketones
- ketonuria
- when ketonemia >70mg/dL exceeds renal threshold
- ketones react with sodium nitroprusside => colour
urine nitrite
- identify asymptomatic UTI: NO3 -> NO2 (dye colour increases)
- but not all bacteria have nitrate reductase
- false positives: foods or dyes => red
leukocyte esteerase
- detects intact and lysed WBCs; infection; increased dye colour
- normal is <10 WBCs/uL
- pathology is > 20 BCs/uL (bacteria, pyuria)
these often detect asymptomatic UTI
urine nitrite
leukocyte esterase
urine blood
- intact RBCs in urine = hematuria
- early indicator of disease but not severity
urine bilirubin, urobilinogen
- hemoglobin -> heme -> bilirubin -> urobilinogen
indicator of liver disease (should be REALLY LOW; should not be a colour change on dipstick)
urine proteins
- normal <150 mg/day
- proteinuria = increased protein in urine due to glomerular or tubular damage
- detected by indicator dye tetrabromophenol blue
- FIRST indication of renal disease
> diabetic nephropathy
> edema and nephrotic syndrome (up to 5 g/day!) - albumin, Bence-Jones proteins, uromodulin mucoproteins, B2-microglobulin and other small MW proteins
Albustix detect
- for albumin only; >50 mg/day
- qualitative dipstick tests may miss low [albumin]; most only detect >250 mg/day
- microalbuminuria = 15-300 mg/day
albuminuria
- increase urine [albumin] more important than total urine protein
- powerful indicator of diabetic nephropathy; glomerulus affected first
Bence Jones proteins
- low MW proteins arising from overproduction of light chain kappa and lambda immunoglobulin para-proteins
- precipitate at 40-60 Cc
- redissolve at 10C
most abundant protein in urine
- uromodulin (Tamm-Horsfall) mucoprotein
- 20-70 mg/day
- mucoprotein (85kD): 30% carb (forms a gel)
> affects water impermeability (mutants cant concentrate urine)
> secreted by renal distal tubule and collecting duct cells - inhibits viral hemagglutination, formation of calcium stone, development of UTI
B2 microglobulin and other small MW proteins
- present due to defective tubule reabsorption due to tubule damage arising from:
> heavy metal poisoning (lead)
> Wilson’s disease: tissue deposition of copper
> Fanconi’s syndrome: proximal tubule malabsorption
aminoaciduria
- normal is 1-2% of total nitrogen in urine due to AA
- overflow aminoaciduria = increase [plasma amino acid]
> inborn error
> excessive breakdown of body protein
> increase protein diet - renal aminoaciduria: not absorbed in tubule ; renal tubular disease
ig light chain damage nephrons when they deposit in ells and become trapped in hyaline casts = block tubules
Bence Jones proteins
a defense protein
- uromodulin
- inhibit mechanisms of pathogens; prevents formation of stone
non-protein nitrogen
- metabolic waste
> majority from protein metabolism as urea; remainder from…
> muscle turnover as creatinine
>nucleic acid (purine) metabolism as uric acid
marker of impaired renal function, ___ is cleared from the blood by kidneys
NPN = non-protein nitrogen
source of urea
- product of protein breakdown in liver
AAas -> ammonia
-> urea cycle -> urea
urea in liver failure
urea formation is impaired
what does an increase in serum [urea] mean?
decrease in renal clearance
marker of renal function!!!
- not detected until GFR function is decreased by 25-50%
product of muscle turover
creatinine (creatine phosphate)
increase serum creatinine
- significantly impaired renal function
- >75% function lost!
creatinine
- constant production varies with muscle mass; not activity
- cleared from blood by the kidney
- ALWAYS present in urine at constant rate (useful to use as reference)
- serum levels not affected by diet
T or F. Serum creatinine alone is a sensitive indicator of renal function
F!
- clearance must drip to 25% of normal before serum creatinine is increased so not very sensitive
Jaffe reaction
creatinine and picrate ion (OH-) => creatinine picrate (A500); a yellow colour
- suitable for urine, protein-free filtrate of plasma or serum
- subject to interferences
- negative interference with bilirubin (yellow) but can be managed w buffers or ferricyanide to oxidize to biliverdin
enzyme-linked rxns for determining creatineine
NADH ; inversely proportional
the more creatinine the less absorption
uric acid
NPN waste product derived from purine nucleic acids
- adenosine and guanosine
increase in [uric acid]
impaired renal function or …
forms of uric acid
keto form and lactim (enol uric acid; weakly acidic and forms salts with Na+ and K+)
this eliminates nitrogen from purine metabolism
uric acid
uricase or urate oxidase
- converts uric acid to allantoin (less liquid waste)
- step missing in humans
what causes hyperuricemia?
- decrease renal excretion
- acidosis
- enhanced cellular breakdown
- increased dietary intake of precursors (rich man’s disease; organ meats?)
- inborn error: Lesch-Nyhan syndrome (self-mutilation)
> enzyme def in uric acid metabolism - gout
what is gout?
- painful!
- 3-25x increase in plasma uric acid
> deposits in joints - rich man’s disease (diet)
- neuts ingest urate crystals -> chemotactic factor -> arthritis; supersaturation of uric acid = crystals
what can gout be due to?
- deficiency in plasma urate binding protein
- local effects of pH, cold, trauma
uricosuria
- high urine [uric acid]
- increased uric acid production => renal excretion
- poor water solubility => urate crystals in urine
> at low pH soluble Na+ and K+ salts => precipitate = stones - lithium sometimes treatment
- influenced by diet
lithium urate
most soluble salt and can promote uric acid excretion
uric acid methodology
HPLC methods - reversed-phase columns (retention time <6 min)
uricase-catalyzed oxidation
> advantage = specific and can be done directly on serum without protein precipitation
- inversely proportional (high activity of enzyme means that lots of urate present and this is measured at A292 so decrease in absorbance bc converted to allantoin)
peroxide coupling from uricase oxidation to methanol oxidation = chromagen; directly proportional (visible light)
