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RENAL FUNCTION Study Guide Study Guide

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RENAL FUNCTION. Study Guide. Module Focus. The kidney plays a major role in the maintenance of fluid and electrolyte balance. elimination of nitrogenous (nitrogen containing ) waste products of protein catabolism (breakdown) Urea or BUN (blood urea nitrogen) Creatinine - PowerPoint PPT Presentation

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Page 1: RENAL FUNCTION

RENAL FUNCTION

Study GuideStudy Guide

Page 2: RENAL FUNCTION

Module FocusModule Focus

The kidney plays a major role in the maintenance of fluid and electrolyte balance. elimination of nitrogenous (nitrogen containing)

waste products of protein catabolism (breakdown)

Urea or BUN (blood urea nitrogen)Creatinine

The kidneys also synthesize and secrete certain hormones.

Page 3: RENAL FUNCTION

NEPHRONNEPHRONAfferent arteriole:Afferent arteriole: the kidney the kidney receives receives 1200 – 1200 – 1500 ml of blood 1500 ml of blood per minuteper minute

Page 4: RENAL FUNCTION

GLOMERULUS First part of nephronFirst part of nephron ““glomus”glomus” means ball means ball

of yarnof yarn Capillary tuftCapillary tuft

Function:Function: Filters blood blood

Allows smaller subtances that are <70,000 MW to pass from blood to tubular filtrate

Filters 125 – 130 ml of plasma per minute “glomerular filtration rate” or GFRGFR

Conserves most proteins or protein bound substances such as blood cells which are too large to be filtered

Filtrate = “cell-free fluid”

Page 5: RENAL FUNCTION

BOWMAN’S CAPSULE Extended end of Extended end of

renal tubulerenal tubule Contains Contains ultrafiltrate ultrafiltrate

of plasmaof plasma

Page 6: RENAL FUNCTION

PROXIMAL TUBULESPROXIMAL TUBULES Reabsorbs or Reabsorbs or returns valuable substances back returns valuable substances back

into bloodinto blood Returns 75-80% of Returns 75-80% of HH22OO Returns amino acids & vitaminsReturns amino acids & vitamins Ions such as Ions such as sodium, potassiumsodium, potassium, chloride, , chloride,

bicarbonate, magnesium & calciumbicarbonate, magnesium & calcium Returns Returns “renal threshold”“renal threshold” substances such as substances such as

glucoseglucose as long as the maximum concentration as long as the maximum concentration is not exceeded in the plasma (160 – 180 is not exceeded in the plasma (160 – 180 mg/dl) the mg/dl) the excess excess the tubules cannot reabsorb the tubules cannot reabsorb will spill into the urinewill spill into the urine

Page 7: RENAL FUNCTION

PROXIMAL TUBULESPROXIMAL TUBULES

ExcretesExcretes waste productswaste products into tubular into tubular lumen lumen (urine)(urine) Urea (BUN)Urea (BUN) CreatinineCreatinine

SecretesSecretes waste products such as waste products such as hydrogen ionshydrogen ions and certain drugs from and certain drugs from the the blood blood into the tubular lumen into the tubular lumen (urine)(urine)

Page 8: RENAL FUNCTION

LOOP OF HENLELOOP OF HENLE

Concentrates filtrateConcentrates filtrate and adjusts urine and adjusts urine osmolalityosmolality

Descending loop is permeable to waterDescending loop is permeable to water Ascending loop is impermeable to waterAscending loop is impermeable to water

Page 9: RENAL FUNCTION

DISTAL TUBULESDISTAL TUBULES Small adjustments are made to achieve electrolyte Small adjustments are made to achieve electrolyte

and acid-base homeostasisand acid-base homeostasis The hormone The hormone aldosteronealdosterone is secreted by the is secreted by the

adrenal cortex in response to a decreased blood adrenal cortex in response to a decreased blood flowflow

Aldosterone stimulates the reabsorption of sodium Aldosterone stimulates the reabsorption of sodium and the loss of potassiumand the loss of potassium

sodium levels in bloodsodium levels in blood potassium and hydrogen levels in bloodpotassium and hydrogen levels in blood

Reabsorption of more water and bicarbonate also Reabsorption of more water and bicarbonate also take placetake place

Elimination of ammonia, hydrogen ions and uric Elimination of ammonia, hydrogen ions and uric acid acid

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COLLECTING DUCTSCOLLECTING DUCTS Determines final urine Determines final urine osmolalityosmolality or or

concentrationconcentration Antidiuretic hormone (ADH)Antidiuretic hormone (ADH) is secreted is secreted

by the posterior pituitary gland in response by the posterior pituitary gland in response to an increase in blood osmolality or to an increase in blood osmolality or decrease in blood volume.decrease in blood volume.

ADH stimulates water reabsorptionADH stimulates water reabsorption by by making the walls permeable to water.making the walls permeable to water.

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FUNCTIONS OF THE KIDNEYFUNCTIONS OF THE KIDNEY

Water balanceWater balance maintained by: maintained by: Ingestion of waterIngestion of water Excretion & reabsorption of water in renal tubules under Excretion & reabsorption of water in renal tubules under

the influence of ADHthe influence of ADH

Electrolyte balanceElectrolyte balance Sodium, potassium, phosphate, calcium and magnesiumSodium, potassium, phosphate, calcium and magnesium Maitained by tubule reabsorption under influence of Maitained by tubule reabsorption under influence of

aldosteronealdosterone

Acid-Base balanceAcid-Base balance Conserve bicarbonate Conserve bicarbonate (HCO3(HCO3--)) Excretes hydrogen ions Excretes hydrogen ions (H(H++))

Page 12: RENAL FUNCTION

ELIMINATION OF NON-PROTEIN NITROGEN SUBSTANCES

NPN substancesNPN substances = compounds that = compounds that contain nitrogen, but are not considered contain nitrogen, but are not considered proteinsproteins UreaUrea (also known as blood urea (also known as blood urea

nitrogen nitrogen “BUN”)“BUN”) CreatinineCreatinine AmmoniaAmmonia Uric acidUric acid

Page 13: RENAL FUNCTION

SYNTHESIS OF HORMONESSYNTHESIS OF HORMONES

ReninRenin – which is a vasoconstrictor that aids in – which is a vasoconstrictor that aids in the regulation of sodium balance and blood the regulation of sodium balance and blood pressurepressure

Erythropoietin Erythropoietin – which increases hemoglobin – which increases hemoglobin production by stimulating RBC productionproduction by stimulating RBC production

1,25-dihydroxycholecalciferol,1,25-dihydroxycholecalciferol, the active form of the active form of Vitamin D, Vitamin D, which facilitates calcium absorption which facilitates calcium absorption from the intestinefrom the intestine

ProstaglandinsProstaglandins – which affect renal blood flow – which affect renal blood flow

Page 14: RENAL FUNCTION

URINALYSIS

Physical properties Physical properties Chemical analysisChemical analysis

pHpH ProteinProtein GlucoseGlucose BilirubinBilirubin bloodblood

Microscopic analysisMicroscopic analysis CellsCells CrystalsCrystals CastsCasts

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CHEMISTRY TESTSCHEMISTRY TESTS Blood urea nitrogen Blood urea nitrogen

(BUN)(BUN) Major waste product of Major waste product of

protein breakdownprotein breakdown 10 – 20 mg/dl10 – 20 mg/dl

CreatinineCreatinine Waste product formed Waste product formed

in in muscle muscle from creatine from creatine phosphatephosphate

Serum = Serum = 1.0 mg/dl1.0 mg/dl & & urine = urine = 1 – 2 grams1 – 2 grams per per day (constant amount)day (constant amount)

BUN/Creatinine BUN/Creatinine Ratio Ratio Calculation or Calculation or

comparisoncomparison The ratio of The ratio of

BUN to serum BUN to serum creatininecreatinine

Normally = Normally = 10:1 10:1 to 20:1 ratioto 20:1 ratio

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CREATININE CLEARANCECREATININE CLEARANCE Measurement or calculation of the Measurement or calculation of the

glomerular filtration rate (GFR)glomerular filtration rate (GFR) Considered the Considered the most sensitive chemicalmost sensitive chemical

testtest for assessing kidney function for assessing kidney function Collect a Collect a 24 hour or timed urine 24 hour or timed urine

specimenspecimen & a & a blood specimenblood specimen from the from the patientpatient

Measure the Measure the creatininecreatinine in the serum & in the serum & urine specimenurine specimen

Calculate the clearanceCalculate the clearance

Page 17: RENAL FUNCTION

CLEARANCE CALCULATIONSCLEARANCE CALCULATIONS

Urine creatinine mg/dlUrine creatinine mg/dl X Volume of Urine in ml/minute X Volume of Urine in ml/minute

Serum creatinine mg/dlSerum creatinine mg/dl

= Creatinine Clearance in ml per minute= Creatinine Clearance in ml per minute

Reference RangesReference Ranges = approximately 125 ml/minute = approximately 125 ml/minute

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Page 19: RENAL FUNCTION

URIC ACIDURIC ACID

Not typically used as a renal function testNot typically used as a renal function test Because it is a nonprotein nitrogen waste Because it is a nonprotein nitrogen waste

substance, it will be increased in serum if substance, it will be increased in serum if there is any type of renal dysfunctionthere is any type of renal dysfunction

Useful in the diagnosis of goutUseful in the diagnosis of gout – arthritic – arthritic condition where uric acid deposits in joints condition where uric acid deposits in joints & also produces renal calculi& also produces renal calculi

Page 20: RENAL FUNCTION

BLOOD UREA NITROGENBLOOD UREA NITROGENBUN OR UREABUN OR UREA

Composition:Composition:

OO

NNHH22 – C – – C – NNHH22

To convert BUN to Urea,To convert BUN to Urea,

Multiply the BUN value by Multiply the BUN value by 2.14 2.14

Since Since 60 (urea) 60 (urea) = 2.14= 2.14

28 (BUN)28 (BUN)

Molecular weightMolecular weight

NN = 14 x 2 = = 14 x 2 = 2828

C = 12C = 12

O = 16O = 16

H = 1 x 4 = 4H = 1 x 4 = 4

TotalTotal = = 60 gms60 gms

Page 21: RENAL FUNCTION

SOURCE OF UREASOURCE OF UREA MajorMajor excretory product of excretory product of proteinprotein catabolismcatabolism.. Formed in the Formed in the LIVERLIVER from carbon dioxide and from carbon dioxide and

ammonia through the urea cycle.ammonia through the urea cycle.

COCO22 + + NHNH33 = = UreaUrea Excreted by the kidneysExcreted by the kidneys

Urea is a small molecule so it is filtered by the Urea is a small molecule so it is filtered by the glomeruliglomeruli

Approximately 40 – 70% is reabsorbed by the Approximately 40 – 70% is reabsorbed by the tubules (the amount reabsorbed is dependent tubules (the amount reabsorbed is dependent upon the rate of urine flow)upon the rate of urine flow)

Page 22: RENAL FUNCTION

UREASE METHOD1. The enzyme 1. The enzyme urease urease hydrolyzes the hydrolyzes the urea urea in the in the

patient specimen to form COpatient specimen to form CO22 & ammonium (NH & ammonium (NH44) )

urease urease UREA UREA NHNH44 + CO + CO22

2. The ammonium is quantitated utilizing the enzyme 2. The ammonium is quantitated utilizing the enzyme glutamate dehydrogenase (GLDH) that reduces glutamate dehydrogenase (GLDH) that reduces the coenzyme the coenzyme NADH to NADNADH to NAD with causes a with causes a decrease in absorbance that is measured at decrease in absorbance that is measured at 340nm.340nm.

GLDH GLDH NHNH44 + + -ketoglutarate + -ketoglutarate + NADH NADNADH NAD + glutamic acid + H + glutamic acid + H22OO

Page 23: RENAL FUNCTION

REFERENCE RANGES

BUN is approximately BUN is approximately 10 – 20 mg/dl10 – 20 mg/dl in in serumserum

European labs correctly express BUN as European labs correctly express BUN as Urea.Urea. To convert, multiply BUN by To convert, multiply BUN by 2.142.14 Example:Example: BUN = 15mg/dl BUN = 15mg/dl

Urea Urea = 15 x 2.14 = = 15 x 2.14 =

Page 24: RENAL FUNCTION

CLINICAL INTERPRETATIONCLINICAL INTERPRETATIONINCREASES INCREASES

Prerenal Factors Any condition that causes decreased renal

perfusion (blood flow)Congestive heart failure (CHF)

Renal Factors – any renal diseases or disorders Postrenal Factors -Obstruction such as renal calculi High protein diet “Dr. Atkin’s diet” will cause mild

increases since urea comes from the breakdown of protein.

Cortisol therapy may also cause mild increases.

Page 25: RENAL FUNCTION

DECREASES IN BUN

Decreases in BUN are rareDecreases in BUN are rare & usually & usually insignificantinsignificant

PregnancyPregnancy Starvation Starvation Severe liver disease - Severe liver disease - synthesis synthesis

Page 26: RENAL FUNCTION

CLINICAL INTERPRETATION

BUN is a more sensitiveBUN is a more sensitive indicator or renal indicator or renal function because it function because it rises earlier and more rises earlier and more rapidly than creatinine.rapidly than creatinine. However, it requires approximately However, it requires approximately 75%75% loss loss

of nephron functionof nephron function before either BUN or before either BUN or creatinine serum values increase.creatinine serum values increase.

BUN is BUN is NOT NOT specificspecific because because diet (high diet (high protein)protein) and cortisol therapy may affect results and cortisol therapy may affect results and and cause false increases.cause false increases.

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CREATININECREATININESOURCESOURCE

Waste product Waste product formed in muscleformed in muscle from from creatine creatine phosphatephosphate When needed for energy, creatine phosphate and When needed for energy, creatine phosphate and

ADP are converted to creatine & ATPADP are converted to creatine & ATP A small portion of creatine phosphate loses its A small portion of creatine phosphate loses its

phosphate and creatinine is formed.phosphate and creatinine is formed. Creatinine is excreted in the urine and is Creatinine is excreted in the urine and is NOT NOT usually usually

reabsorbedreabsorbed The The amount of creatinine formed and excretedamount of creatinine formed and excreted per per

day is a function of muscle mass. Typically normal day is a function of muscle mass. Typically normal individuals excrete individuals excrete 1 to 2 grams per day1 to 2 grams per day of creatinine. of creatinine.

Page 28: RENAL FUNCTION

METHODS ColorimetricColorimetric: : Jaffe ReactionJaffe Reaction

NaOH creatinine + picric acid alkaline picratealkaline picrate

(reddish-orange complex)(reddish-orange complex) Noncreatinine chromagens (color-producing substances) such as Noncreatinine chromagens (color-producing substances) such as

glucose, ketones and vitamin C may interfere with this reactionglucose, ketones and vitamin C may interfere with this reaction Jaffe KINETIC method modification was designed to monitor the Jaffe KINETIC method modification was designed to monitor the

rate of the reaction at selected time intervals to avoid picking up rate of the reaction at selected time intervals to avoid picking up noncreatinine chromagens. (Typically 25 – 60 seconds)noncreatinine chromagens. (Typically 25 – 60 seconds)

Enzymatic:Enzymatic: Creatinine aminohydrolase Creatinine aminohydrolase A variety of coupled enzymatic methods are available.A variety of coupled enzymatic methods are available.

Page 29: RENAL FUNCTION

REFERENCE RANGES

SerumSerum = = 0.8 – 1.4 mg/dl0.8 – 1.4 mg/dl UrineUrine = = 1 – 2 grams per day1 – 2 grams per dayFYI: FYI: A serum creatinine value of A serum creatinine value of 4mg/dl4mg/dl is is

equivalent to a equivalent to a reduction of GFR to 15 – reduction of GFR to 15 – 20% of normal.20% of normal.

An An 8 mg/dl8 mg/dl value = a reduction of GFR to value = a reduction of GFR to 6 – 10% of normal.6 – 10% of normal.

Page 30: RENAL FUNCTION

CLINICAL INTERPRETATION

INCREASESINCREASES Any renal factorsAny renal factors Creatinine is Creatinine is NOTNOT affected by diet affected by diet Creatinine is Creatinine is NOTNOT typically reabsorbed by typically reabsorbed by

the tubulesthe tubules Creatinine levels reflect the glomerular Creatinine levels reflect the glomerular

filtration rate filtration rate (GFR)(GFR)

Page 31: RENAL FUNCTION

DECREASESDECREASES

No medical significanceNo medical significance

Page 32: RENAL FUNCTION

CLINICAL INTERPRETATION

Creatinine is Creatinine is more specific than BUN more specific than BUN since it is not affected by nonrenal factorssince it is not affected by nonrenal factors..

Creatinine is Creatinine is not as sensitive as BUNnot as sensitive as BUN since serum creatinine since serum creatinine levels rise slowerlevels rise slower than BUN levels.than BUN levels.

Remember:Remember: Creatinine serum levels are Creatinine serum levels are not above normal until ½ to ¾ of kidney not above normal until ½ to ¾ of kidney function is lost.function is lost.

Page 33: RENAL FUNCTION

BUN-CREATININE RATIOBUN-CREATININE RATIO

Purpose:Purpose: Calculation/comparison that compares Calculation/comparison that compares

the patient’s BUN to their creatinine the patient’s BUN to their creatinine valuevalue

Quality control purposesQuality control purposes Differential diagnosisDifferential diagnosis

Page 34: RENAL FUNCTION

EXAMPLEEXAMPLE

If a patient’s BUN is approximately If a patient’s BUN is approximately 10 – 1510 – 15 mg/dl,mg/dl, their creatinine should be their creatinine should be approximately approximately 1.0mg/dl.1.0mg/dl.

This would be equivalent to a This would be equivalent to a 10:1 to 15:1 10:1 to 15:1 ratio.ratio.

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REFERENCE VALUESREFERENCE VALUES

10:1 to 15:1 ratio is considered normal10:1 to 15:1 ratio is considered normal Normal ratios are usually observed in Normal ratios are usually observed in

renal diseasesrenal diseases.. Example:Example: If a patient’s BUN is If a patient’s BUN is

50 mg/dl,50 mg/dl, their creatinine would be their creatinine would be approximately approximately 5.0 mg/dl.5.0 mg/dl.

Page 36: RENAL FUNCTION

CLINICAL INTERPRETATIONCLINICAL INTERPRETATION

INCREASES:INCREASES: A 20:1 to 30:1 ratio is often due to A 20:1 to 30:1 ratio is often due to

prerenal factorsprerenal factors Decreased renal perfusion (blood flow Decreased renal perfusion (blood flow

to the kidneys) such as:to the kidneys) such as:Congestive heart failureCongestive heart failureShock, etc.Shock, etc.Causes a >40% reabsorption of urea Causes a >40% reabsorption of urea

occurs, but NOT creatinineoccurs, but NOT creatinine

Page 37: RENAL FUNCTION

CREATININE CLEARANCECREATININE CLEARANCE

Estimates the Estimates the Glomerular Filtration RateGlomerular Filtration Rate (GFR) (GFR) by measuring the serum/plasma creatinine level by measuring the serum/plasma creatinine level and its rate of excretion into the urine.and its rate of excretion into the urine.

Clearance indicates the number of milliliters of Clearance indicates the number of milliliters of plasma from which the kidney can remove all of a plasma from which the kidney can remove all of a given substance in one minute.given substance in one minute.

The The normal GFRnormal GFR is approximately is approximately 125 ml/minute125 ml/minute..

Page 38: RENAL FUNCTION

CLEARANCE REQUIREMENTSCLEARANCE REQUIREMENTS

Substance must be Substance must be filtered through the filtered through the glomeruliglomeruli

Essentially Essentially no absorbance or secretionno absorbance or secretion must take place in the tubules.must take place in the tubules.

Substance must Substance must exist in the same formexist in the same form in in the blood and the urine.the blood and the urine.

Ideally, an Ideally, an endogenousendogenous (body-made) (body-made) substancesubstance should be utilized. should be utilized.

Page 39: RENAL FUNCTION

PROCEDUREPROCEDURE1.1. Collect a Collect a timed urine specimentimed urine specimen ( (usually usually

a 24 houra 24 hour) from the patient.) from the patient.a)a) Record the time period of the collectionRecord the time period of the collectionb)b) Measure and record the total volume of the urine Measure and record the total volume of the urine

specimenspecimen

2.2. Collect a Collect a blood specimenblood specimen during the during the time of the urine collection period.time of the urine collection period.

3.3. Measure the urine and serum creatinine Measure the urine and serum creatinine in mg/dl.in mg/dl.

4.4. Calculate the clearance.Calculate the clearance.

Page 40: RENAL FUNCTION

Calculate the rate of urine flow or “VOLUME” in ml/minute

Divide the Divide the total volume of the urinetotal volume of the urine specimen by specimen by the number of the number of MINUTES MINUTES in the collection period.in the collection period.

Example: Example: The total volume of a 24hr urine specimen

was 1500ml The number of minutes in a 24hr period

would be 24 x 60 = 1440 minutes Divide 1500ml by 1440 minutes Volume = 1.04 ml/minute

Page 41: RENAL FUNCTION

Clearance CalculationsClearance Calculations

Urine creatinine (mg/dl)Urine creatinine (mg/dl) X X Volume (ml/min)Volume (ml/min)

Serum creatinine (mg/dl)Serum creatinine (mg/dl)

Example: Example: A patient’s serum creatinine was 1.0

mg/dl and their urine creatinine was 100 mg/dl. The volume of the 24 hr urine specimen was 1500 ml or 1.04 ml/minute.

Clearance =

100 mg/dl X 1.04 ml/min = 104 ml/minute 1.0 mg/dl

Page 42: RENAL FUNCTION

REFERENCE VALUESREFERENCE VALUES

Serum creatinineSerum creatinine = = 0.8 – 1.4 mg/dl0.8 – 1.4 mg/dl Urine creatinineUrine creatinine = = 1- 2 grams per day or 1- 2 grams per day or

100 mg/100 ml100 mg/100 ml Total volume = 1000 – 2000 ml/dayTotal volume = 1000 – 2000 ml/day Creatinine ClearanceCreatinine Clearance

Males: 75 – 140 ml/minuteMales: 75 – 140 ml/minute Females: 70 – 130 ml/minuteFemales: 70 – 130 ml/minute

Page 43: RENAL FUNCTION

CLINICAL INTERPRETATION

Remember:Remember: You are looking for You are looking for increased serum valuesincreased serum values due to the failure of the kidneys to excrete creatinine. due to the failure of the kidneys to excrete creatinine. This will cause a This will cause a decrease in urine creatininedecrease in urine creatinine as well as as well as a a decreased clearance values.decreased clearance values.

DECREASED CLEARANCE VALUESDECREASED CLEARANCE VALUES Acute or chronic damage to the glomeruli Creatinine clearance is the MOST SENSITIVE chemical

indicator of assessing renal function. (more sensitive than serum BUN or serum creatinine)

Page 44: RENAL FUNCTION

SOURCES OF ERRORSOURCES OF ERROR Error in Error in collection of urine specimencollection of urine specimen CalculationsCalculations If If clearance values are decreasedclearance values are decreased, but the , but the

patient’s patient’s serum creatinine is normalserum creatinine is normal, , check:check: Clearance calculationsClearance calculations Urine volume and timingUrine volume and timing

Incomplete voidingIncomplete voiding Incomplete timingIncomplete timingLoss of some urine specimenLoss of some urine specimen Incorrect volume measurementIncorrect volume measurement

Urine & serum creatinine valuesUrine & serum creatinine values

Page 45: RENAL FUNCTION

Increased Clearance Values

No medical significanceNo medical significance Suspect error in collection of urineSuspect error in collection of urine

specimenspecimen

Page 46: RENAL FUNCTION

Correction of Clearance for Body Surface Area

Purpose:Purpose: Since creatinine is a function of muscle mass, Since creatinine is a function of muscle mass, correction is essential if a patient is correction is essential if a patient is unusually largeunusually large or or smallsmall such as a such as a pediatric patient.pediatric patient.

Procedure:Procedure:1.1. Obtain the height & weight of the patient.Obtain the height & weight of the patient.

2.2. Use a nomogram such as the one in your text or study Use a nomogram such as the one in your text or study guide to obtain the guide to obtain the body surface areabody surface area of the patient in of the patient in square meters.square meters.

3.3. The body surface area of the The body surface area of the averageaverage patient is patient is assumed to be assumed to be 1.73 square meters.1.73 square meters.

4.4. Use the following formula to obtain the Use the following formula to obtain the corrected corrected clearance:clearance:

Clearance (before correction) X Clearance (before correction) X 1.73 M1.73 M22

Body surface area of Body surface area of patient in Mpatient in M22

Page 47: RENAL FUNCTION

URIC ACIDSource:Source: Breakdown of nucleic acids such as RNA & DNABreakdown of nucleic acids such as RNA & DNA End product of End product of purinepurine metabolism. metabolism. Purines = nitrogen containing constituents of Purines = nitrogen containing constituents of

certain coenzymes and certain coenzymes and nucleic acids.nucleic acids. Derived from endogenous (body made) and Derived from endogenous (body made) and

exogenous (dietary) nucleoproteins.exogenous (dietary) nucleoproteins. Liver, kidneys & shellfish are rich in Liver, kidneys & shellfish are rich in

nucleoproteins.nucleoproteins.

Page 48: RENAL FUNCTION

URIC ACID METABOLISM

Uric acid is synthesized in the liver from the Uric acid is synthesized in the liver from the breakdown of nucleic acids.breakdown of nucleic acids.

90 – 95% is filtered through the glomeruli.90 – 95% is filtered through the glomeruli. Uric acid is Uric acid is relatively insolublerelatively insoluble and will precipitate and will precipitate

out of solution if concentration in plasma is > 6.5 out of solution if concentration in plasma is > 6.5 mg/dl forming mg/dl forming deposits in jointsdeposits in joints as well as as well as renal renal calculi (kidney stones).calculi (kidney stones).

Mammals other than man are usually capable of Mammals other than man are usually capable of oxidizing uric acid to oxidizing uric acid to allantoinallantoin, which is a more , which is a more soluble compound.soluble compound.

Page 49: RENAL FUNCTION

Methods of Measurement Phosphotungstic method – outdatedPhosphotungstic method – outdated UricaseUricase – enzymatic method is the most – enzymatic method is the most

widely utilizedwidely utilized

URICASEURICASE

Uric acid + OUric acid + O22 + H + H22O Allantoin + O Allantoin + HH22OO22 + CO + CO22

Uric acid is oxidized to allantoin and hydrogen Uric acid is oxidized to allantoin and hydrogen peroxide (Hperoxide (H22OO22) is formed.) is formed.

A coupled enzymatic reaction, utilizing the A coupled enzymatic reaction, utilizing the enzyme enzyme peroxidase,peroxidase, is typically used to quantitate is typically used to quantitate the amount of the amount of hydrogen peroxidehydrogen peroxide produced. produced.

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Reference Ranges

Males:Males: 3.5 – 7.2 mg/dl 3.5 – 7.2 mg/dl Females:Females: 2.6 – 6.0 mg/dl 2.6 – 6.0 mg/dl

Page 51: RENAL FUNCTION

Clinical InterpretationINCREASESINCREASES

GOUT:GOUT: overproduction of uric overproduction of uric acid which is relatively acid which is relatively insoluble and depositis insoluble and depositis in joints causing in joints causing “GOUTY ARTHRITIS”“GOUTY ARTHRITIS”

in plasma uric acid in plasma uric acid may also cause may also cause renal renal calculi to form.calculi to form.

Miscellaneous IncreasesMiscellaneous Increases Increased tissue Increased tissue

breakdown asbreakdown as seen in seen in chemotherapy and chemotherapy and radiation treatment.radiation treatment.

Increased dietary intakeIncreased dietary intake of of foods rich in purines.foods rich in purines.

Decreased excretionDecreased excretion of of uric acid will cause an uric acid will cause an increase in serum levles, increase in serum levles, as seen in renal diseases. as seen in renal diseases. However, uric acid is However, uric acid is not not typically utilized as a renal typically utilized as a renal function test.function test.

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OSMOLALITY

Purpose:Purpose: useful in the useful in the evaluation of evaluation of fluid & fluid & electrolyte balanceelectrolyte balance

Provides an Provides an assessment of the assessment of the hydration statushydration status of a of a patient.patient.

Sodium ionsSodium ions account account for for 90% of osmotic 90% of osmotic pressurepressure..

Osmolality is actually a Osmolality is actually a measurement of the measurement of the TOTALTOTALNUMBER NUMBER of dissolved of dissolved particles per kilogram of particles per kilogram of water.water. The molecular weight, size or The molecular weight, size or

type of particle does not type of particle does not matter.matter.

Osmolality is a more accurate Osmolality is a more accurate reflection of the total number reflection of the total number of dissolved particles in a of dissolved particles in a solution than the specific solution than the specific gravity.gravity.

Page 53: RENAL FUNCTION

OSMOMETRY OSMOMETRY Any substance dissolved in a solution will Any substance dissolved in a solution will

do the following:do the following: Increase the osmotic pressure of the Increase the osmotic pressure of the

solutionsolution Elevate the boiling point (Elevate the boiling point (Have you ever Have you ever

made fudge?)made fudge?) Decrease the vapor pressureDecrease the vapor pressure Lower/depress the freezing pointLower/depress the freezing point (Have (Have

you ever made popsicles or frozen you ever made popsicles or frozen daiquiris?) daiquiris?) They take longer to freeze They take longer to freeze than ice cubes or water.than ice cubes or water.

Page 54: RENAL FUNCTION

FREEZING POINT DEPRESSION FREEZING POINT DEPRESSION METHODMETHOD

The more particles in a solution (the more The more particles in a solution (the more concentrated), the concentrated), the LOWER LOWER will be its will be its freezing freezing point.point.

The osmometer actually superfreezes urine or The osmometer actually superfreezes urine or serum belong its freezing point and then brings it serum belong its freezing point and then brings it back to its actual freezing point.back to its actual freezing point.

One moleOne mole of each ionic or nonionic of each ionic or nonionic particle/kilogram of water particle/kilogram of water lowers the freezing lowers the freezing point by 1.86C.point by 1.86C.

Page 55: RENAL FUNCTION

REFERENCE VALUESREFERENCE VALUES

Serum:Serum: 275 – 300 mOsm/kg 275 – 300 mOsm/kg

24hr urine:24hr urine: 300 – 900 mOsm/kg 300 – 900 mOsm/kg

Random urine: 40 – 1350 mOsm/kgRandom urine: 40 – 1350 mOsm/kg The The ratio of urine osmolality to serumratio of urine osmolality to serum osmolality: osmolality:

Urine should be at least as concnetrated as Urine should be at least as concnetrated as serum if not 3X as concentrated.serum if not 3X as concentrated.

Ratio = Ratio = 1.0 – 3.01.0 – 3.0 Example:Example: urine = 900 urine = 900 Ratio Ratio = = 3.03.0

serum = 300serum = 300

Page 56: RENAL FUNCTION

CLINICAL INTERPRETATIONCLINICAL INTERPRETATION

Increased valuesIncreased values DehydrationDehydration Hypernatremia (Hypernatremia ( sodium in plasma sodium in plasma)) Hyperglycemia, azotemia (Hyperglycemia, azotemia ( BUN & BUN &

creatinine), alcohol ingestioncreatinine), alcohol ingestion Decreased valuesDecreased values

OverhydrationOverhydration Hyponatremia Hyponatremia (( sodium in plasma) sodium in plasma)

Page 57: RENAL FUNCTION

CALCULATED OSMOLALITYCALCULATED OSMOLALITY If an osmometer is not available, the osmolality If an osmometer is not available, the osmolality

can be calculated if the serum sodium, glucose & can be calculated if the serum sodium, glucose & BUN results are available. BUN results are available.

Osmol Gap: Osmol Gap: The difference between the calculated The difference between the calculated

osmolality and the measured osmolality.osmolality and the measured osmolality. If the gap is >0, may indicate the presence of a If the gap is >0, may indicate the presence of a

volatile substance such as ethanol, methanolvolatile substance such as ethanol, methanol or ethylene glycol (antifreeze).or ethylene glycol (antifreeze).