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Subject: Pathology Topic: (CP) Renal Function Tests Lecturer: Luis P. Cruz.

MD, FPSP, FPSO Date of Lecture: January 31, 2012 Transcriptionist: JE Rivera Editor: Melodicine Pages: 4

SY 2011-2012

KIDNEY FUNCTIONS 1. Excre tory 2. Regulat ory Removal Of Waste Products Of Metabolism (Urea, Creatinine,Uric Acid And Amino Acids) Involves Homeostatic Control Through Reabsorption And Secretion Processes That Establish The Equilibrium Of Water And Electrolytes Thus Balancing The Acid And Base Levels Includes Both Primary And Secondary Activity In The Control Of Hormone Production Vitamin D Erythropoietin Renin/Angiotensin/Aldosterone Axis Tied Up To The Formation Of Urine Through: Filtration Reabsorption Secretion Excretion

3. Endo crine Funct ions

*80% Destruction Of The Nephrons Will Impair Kidney Function RENAL FUNCTION CATEGORIES Predominantly Glomerular Function Severe Glomerular or Tubular Damage or Both Predominantly Tubular Function Clearance Test Blood Urea Nitrogen Serum Creatinine Phenolsulfonphthalein Excretion Specific Gravity Osmolality IVP

Concept Of Clearance Relates The: Rate Of Urinary Excretion Of Material (Ux) Within A Given Volume (V) To The Plasma Concentration Of That Material(Px) *Expressed In Ml/Min Clearance = (Uxv) / P

MEASUREMENT OF GLOMERULAR FILTRATION RATE (GFR) Measurement Of Substance Clearance Approximates Patients GLOMERULAR FILTRATION RATE. GFR, 120ml/Min Substance Must Be Filtered Exclusively By The Glomerulus And Not Reabsorbed, Secreted, Synthesized Or Degraded In Other Parts Of The Nephron Ultrafiltrate Of Plasma , Similar In Composition But Almost Free Of Protein Urinary Protein Excretion Is Less Than 150 Mg/24 Hrs

RENAL FUNCTION TESTS Assessment Of Glomerular Permeability Under Normal Conditions , Macromolecules (E.G. Proteins) Are Not Allowed To Be Filtered At The Glomerulus Thus Protein In The Urine Provides An Indication Of Glomerular Basement Membrane Integrity.

1. Diagnostic Tests And Methodologies Test Urea Method INDIRECT Step 1. Urease Hydrolyses Urea Step 2. Quantitate Ammonium Ion Most Frequently Used Chromogens That React With Picrate Kinetic Assays Improves Specificity Interference Ammonia Comments

ENZYMATIC ASSAY Creatin e JAFFE REACTION; Creatinine And Picrate Form Red-Orange Complex ENZYMATIC Creatinine Aminohydrolase Converts Creatinine To Creatine

Better Specificity

HLPC(High Performance Liquid Chromatography) Uric Acid Phospatungstic Acid (PTA) Reduced By Uric Acid, Forming A Blue Color Reaction Proteins And Lipids Cause Turbidity And Quench Absorbance; Reduction Of PTA Uricase Oxidizes Uric Acid Forming By Either Substance Is Very Carbon Dioxide, Hydrogen Little Peroxide And Allantoin

High Accuracy Infrequently Used Protein Removal; Falsely Elevates Results Most Common; Increases Specificity

1. Summary Of Clearance Tests Test UREA Method Endogenous; Used For GFR Measuring Both Serum And Urine Levels Followed By Clearance Formulas CREATININ E CLEARANC E Endogenous; Used For GFR Measuring Both Serum And Urine Levels Followed By Clearance Formulas; x (Us xV) Cs = 1.73 Ps A Adjustments Comments NOT RELIABLE; Reabsorbed And Secreted

MOST COMMON Little Daily Variation Freely Filtered With Relatively Small Amount Secreted In The Tubules When GFR Is <10ml/Min, Test Is Less Accurate

In The Presence Of Increased Plasma Protein, Secretion Increase Leads To Overestimation Of GFR

INULIN CLEARANC E

Exogenous, Used For GFR Measuring Both Serum And Urine Levels Followed By Clearance Formula

LIMITED USE; Technical; IV Administration Freely Filtered And Not Absorbed Increases Precision REFERENCE METHOD

P-AMINO HIPPURIAT E CLEARANC E

Exogenous Used For Rate Of Renal Flow

UNRELIABILITY* High Extraction Rate Filtered And Secreted Normal: 580-600ml/Min

* In The Presence Of Renal Disease, Accurate Asessment Only If The Kidney Is Functioning Properly

Tubular Function Testing Assess The Ability Of The Tubules To Reabsorb And Secrete Substances During The Formation Of Urine Test Method Comments PHENOLSULFONPTH ALEIN Exogenous, Assess Tubular Secretory Function. Injected, Amount Secreted In Urine Urine Levels Secreted Every 15 Mins Reflects Renal Plasma Flow 94% Secreted; Very Little Filtered; Binds To Albumin. When Kidney Is Normal 2025% Of Injected PSP Should Be Secreted In The 1st 15 Minutes (With Additional 10-15% In The Next 15minutes) With Tubular Damage Reabsorption Is Diminished. Allograft Rejection Diagnosis Cyclosphorine Toxicity And CMV Infection Requires Adequate GFR, Renal Plasma Flow , Tubular Mass And Healthy Tubular Cells To Pump Salts. One Of The Most Sensitive Means Of Evaluating Renal

B2 MICROGLOBULIN

Endogenous; Present On All Nucleated Cells, Filtered But Not Normally Reabsorbed. Serves As Sensitive Indicator Of Renal Excretory Function

OSMOLALITY

Measures The Number Of Particle Present Per Unit Of Solution, Expressed As Millimoles, Per Kilogram Of Water (Mosm/Kg H2O). Ranges From 50-1200 Mosm/Kg Depending On The Patuients Hydration.

Serum: Urine Ratio Determined 1:1 And 1:3, Intact Kidney

Function.

SPECIEFIC GRAVITY

Impaired Concentration, Urine Become Isosthenuric 1.003 1.035 Depending On The Patients Hydration

(Same Specific Gravity As The Original Ultrafiltrate 1.007-1.010)

BUN/ CREATININE RATIO Alteration Causes Decreased Ratio Acute Tubular Necrosis Low Protein Intake Severe Diarrhea And Vomiting Starvation Liver Disease Renal Dialysis* Increased Ratio With NORMAL Creatinine Level (Prerenal Azotemia) Dehydration High Protein Intake Increased Protein Catabolism Muscle Wasting Cortisol Treatment Reabsorption Of Blood Protein After GIT Hemorrhage Decreased Perfusion Of Kidneys (CHF, Shock, Hemorrhage) Increased Ratio With ELEVATED Creatinine Level (Postrenal Azotemia) Normal Ratio With Elevated Urea/Creatinine Levels Obstruction Of Urine Flow Due To: Nephrolithiasis Prostatism GUT Tumors Severe Infection

Comments Less Common Than An Increases Ratio In Health, The Ratio Should Be Between 10:1 To 20:1

*Urea Dialyses Better Than Creatinine And Is Removed From Plasma At A Higher Rate Usually 20:1-30-1 As Urea Is Cleared At A Lower Rate Than Creatinine

Maybe Found When Prerenal Azotemia Is Superimposed On Renal Disease.

End Stage Renal Disease Glomerular Diseases: Acute Nephritic Syndrome RPGN CGN Nephrotic Syndrome

Tubular Disease, Acute Pyelonephritis

BLOOD UREA NITROGEN* Screening Tests ( Urograph /Azostix) Separates Normal ( BUN Level < 20mg/100ml)** Mild Azotemia (20-50mg/100ml) Considerable BUN Elevation (>50mg/100ml)*** * Estimates Renal Function ; Elevation Is AZOTEMIA **7mmol/L ***18mmol/L

AZOTEMIA PRE RENAL

A. Decreased Blood Volume B. Increased Protein Intake Or Endogenous Breakdown

1. Traumatic Shock 2. Hemorrhagic Shock 3. Severe Dehydration 4. Acute Cardiac Decompensation 5. Overwhelming Infection Or Toxemia 6. Excess Intake Of Proteins Or Extensive Breakdown

RENAL

A. Glomerular Or Tubular Damge

1. Chronic Diffuse Bilateral Kidney Disease 2. Acute Tubular Necrosis 3. Severe Acute Glomerular Damage

POSTRENAL

1. Ureteral Or Urethral Obstruction 2. Bladder Tumor 3. Prostate Enlargement / Tumor

Differential Dx Of Azotemia Prerenal Vs. Acute Renal Failure Vs. Chronic Renal Failure Filtered Fraction Of Sodium And Free Water Clearance If BUN As Well As Serum Creatinine Levels Are Elevated Is MORE SUGGESTIVE Of RENAL FAILURE UREMIA Is A SYNDROME , Defined In Clinical Terms BUN Level Of Approximately 100mg/100ml Separates General Category Of Acute Reversible Prerenal Azotemia From The More Prolonged Acute Episodes And Chronic Uremia ___________________________________END TRANSCRIPTION____________________________________ OF

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