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BUN and Creatinine

BUN and Creatinine

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Published by: sarguss14 on Dec 05, 2008
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major excretory product of protein catabolism
45% of total NPNs
Liver --- CO2 & NH3- (Ornithine or Kreb’sHenseleit Cycle)
90% --- kidneys; 10% --- GIT & skin
25 gm of total urinary solids
80-90% of total urinary N
conc. is affected by:
renal function & perfusion
dietary protein intake
level of protein metabolism
N intake & state of hydration > renal fxn
inc. level --- AzotemiaPrerenal Azotemia
inadequate perfusion --- diminished filtration
CHF, shock, dehydration, hemorrhage,diminished blood volume,
High protein diet, muscle wasting,glucocorticoid Tx, fever, stress, burnsRenal Azotemia
primarily diminished glomerular filtration
acute & chronic renal failure, GN, tubularnecrosis, interstitial nephritis, pyelonephritisPostrenal Azotemia
UT obstruction --- inc. in back diffusion of ureafrom renal tubules into circulation
nephrolithiasis, prostatic hypertrophy, GUTtumorsUremia
clinical syndrome with marked inc. levels of urea + acidemia & electrolyte imbalance
N/V, anemia, altered mentation
in excess of 100 mg/dl – 200 mg/dl --- deepstupor to comaLow Levels of Urea
poor nutrition, high fluid intake
pregnancy, severe liver impairment, intake of anabolic hormonesDirect Method
Fearon Rxn --- direct condensation w/ diacetylmonoxime + strong acid = yellow diazinederivative
simple, no interference w/ NH3-
caustic chemicalsIndirect Method
Berthelot Rxn
Urease --- NH4+ & HCO3
NH4+ + nitroprusside --- indophenol
Coupled Enzymatic Rxn
NH4+ --- coupled rxns --- H2O2 +phenol & 4-aminophenazone – quinone-imine dye
Electrochemical approach
rate of inc. conductivity (NH4+ &HCO3)
potentiometric (NH4+ selectiveelectrode)Normal Values
blood: 8-20 mg/dL (2.8-7.1 mmol/L)
urinary excretion: 17-20 g/24h
main storage cmpd of high energy PO4
Arg, Gly, Met
Muscle --- 98% of total creatine pool
filtered by glomeruli but completely reabsorbedby prox tubules
looses water --- cyclized creatinine
inc. serum conc --- ske M necrosis/atrophy,trauma, muscular dystrophies,poliomyelitis,myasthenia gravis, starvation
methyltestosterone use, hyperthyroidism,diabetic acidosis, puerperium
measured by the difference in creatinine before& after conversion of creatine to creatinine ---heatNormal Values
0.2-0.6 mg/dl (15-45 umol/L) – males
0.6-1.0 mg/dl (45-76 umol/L) – females
urinary excretion
0-40 mg/24h (0-0.35 mmol/24h – males
0-100 mg/24h (0-0.88 mmol/24h) -females
once formed can’t be reused --- waste
K excretory rate, 1.6-1.7% of T creatinine ---proportional to M mass
freely filtered by glomerulus but notreabsorbed
inhibited by cimetidine, probenecid, TMP
serum conc is affected by: renal handling,pregnancy, DM, CRF
elevated serum crea --- dec GFR --- impairedrenal fxnMeasurement1.Jaffe Rxn – treatment w/ alkaline picrate solution ---bright orange-red complex
chromogens: glucose, fructose, ascorbic acid,pyruvate, uric acid
inc in T°, pH changes
bilirubin, Hgb, lipemic specimens --- neg
Fuller’s earth or Lloyd’s reagent --- removeinterference
hemolyzed, icteric, lipemic specimens
acetoacetate, acetone, barbiturates,phenolsulfonphthalein, sulfobromophthalein,protein2. Coupled Enzymatic Methods
crea amidohydrolase & crea deaminase --- creacleaving enz
H2O2 + phenol derivative + dye --- colorproduct3. HPLC
high specificity
time consumingNormal Values
0.6-1.2 mg/dl (53-106 umol/L) - males
0.5-1.0 mg/dl (44-88 umol/L) – females
0.3-1.0 mg/dl (26.5-88.4 umol/L) - <12
 T crea excretion
1.0-2.0 g/24h (8.8-17.6 mmol/24h) –males
0.6-1.5 g/24h (5.3-13.2 mmol/24h) -females
serum urea & creatinine
clearance studies
vol of serum/plasma that contained themeasured subs excreted into urine per unit of time
serum clearance is proportional to total # &size of glomeruli, w/c is proportional to renalparenchymal mass
RBF must be appropriate
glomerular filtration must be adequate
renal tubular function should be normal
no significant obstruction to urine outflow
cyclized form of creatinine
related to muscle mass
affected by ingestion of sterilized cannedmeats
active tubular secretion --- counterbalanced byreabsorption in tubulesCreatinine Clearance
N GFR --- crea clearance exceeds inulinclearance by 5-10%
dec. GFR --- crea clearance is largely composedof tubular secretion
glomerular filtration is inc. in NS
drug interferenceMethods of Measuring CreatinineI.Jaffe Reaction
colorimetric determination --- complexof creatinine w/ picric acidII.Ektachem Chemistry Analyzer
enzymatic degradation of creatinine w/creatinase
NH+4 + Bromphenol Blue ---reflectance spectrophotometry
major end product of protein & nucleic acidmetabolism
80% of N excreted
reabsorption & filtration
not reliable estimate of GFR --- ingestion,catabolism, GI losses
inc. --- excess production, diminished renalblood flow (prerenal causes); UT obstruction(postrenal cause); parenchymal renal damage(true renal cause)Urea Clearance Test
infrequently usedMethods of Measuring Urea1.Indirect
generates NH+4 from urea --- urease
NH+4 is coupled w/ glutamatedehydrogenase --- converts A-ketoglutarate to Glu w/ NADH ascofactor --- measuredspectrophotometrically2.Direct
Condensation of urea w/ a diacetyl grp--- chromogen measuredspectrophotometricallyBUN as an indicator of RF
BUN:crea --- 10:1-20:1
renal parenchymal damage --- maintained
inc. ratio --- compromised bld flow --- low urineflow rate (dehydration, CHF, hepato-renalsyndrome, UT obstruction, GI bleeding, fever)
dec. ratio --- low CHON diet, pregnancy, chronichemodialysis
Renal Clearance
General Clearance Formula in mL/min
=Urine substance in mg/dL x Volume inmL/min Serum substance in mg/dL
Clearance in mL/min/std. surface area
=Urine substance x Urine Volume x1.73m2 Serum SubstanceA
Creatinine Clearance
= denotes GFRUrine Creat in mg/dL x Urine Volume inmL/min Serum Creat in mg/dLUrine Creat x Urine Volume x 1.73m2Serum Creat 1440 A
Where 1440 = number of minutes/24 hrs
1.73m2 = BSA of an averagenormal person
A = BSA from a normogram
Estimated Creatinine Clearance
Cockcroft & Gault (1976) withcorrection for age and weight; resultsreported in mL/minMales = (140-age) x Weight inkg (72 xSerum Creat in mg/dL)Females = (140-age) x Weight inkg (0.85 x Serum Creat inmg/dL)
NV males 90-139females80-125slight impairment 52--62.5moderate impairment 28 – 42mild impairment 42–52 severeimpairment < 28
Renal Failure Index (RFI)
=Urine Na in mEq/L x Serum Creatinine inmg/dL Urine Creatinine inmg/dL
RFI <= 1: prerenal azotemia
RFI =1-3: less definitive butusually indicates tubularnecrosis
RFI >= 3: acute tubularnecrosis
Functional Excretion of Sodium (FENa)
Na Clearance x 100Creatinine ClearanceUrine Na x Serum Creat x 100Urine Creat x Serum Na
Renal Function & Nitrogen Balance
Nonprotein Nitrogenous compounds =
Urea (45%)
Amino acids (20%)
Uric acid (20%)
Creatinine (5%)
Creatine (1-2%)
Ammonia (0.2%)
Urea as Blood Urea Nitrogen
Enzymatic assay of NH3 most common
Elevated with primary renal disease
 Jaffe reaction
Elevated with primary renal disease
Uric Acid
Uricase method
Elevated with renal disease,hyperuricemia
BUN:Creatinine ratio= NV 10:1 to 20:1
>20:1 = Prerenal lowperfusion
10:1 to 20:1 = Renal
Stages of Chronic Progressive Renal Disease
StageRenal FunctionRemainingSerum Creatinine(mg/dL)Serum BUN(mg/dL)Decreased renalreserve50-751.0-2.515-30Renal insufficiency25-502.5-6.025-60
FE-Na < 1%FE-Na > 1%
• 10% of cases of nonoliguricATN• pre-renal azotemia• acute glomerulonephritis• early acute urinary tractobstruction• early sepsis• most cases of ATN• after diuretic administration• pre-existing chronic renalfailure• diuresis due to mannitol,glycosuria, bicarbonaturia

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