Renal Functions Lecture-4

1 1 The KidneysDr. Khalid Al-AniDepartment of Clinical PharmacyFaculty of PharmacyLecture-4 Renal FunctionsExcretion of waste -Production of urine-elimination of metabolic end products (Urea, Creatinine, uric acid ..etc)-elimination of foreign materials (Drugs)Control of volume & composition of ECF-Water and electrolyte balance-Acid/Base statusDr. Khalid Al-AniRenal FunctionsEndocrine Functions -renin erythropoietin Calcitriol ( activation of vitamin D)Why Test Renal Function?uTo identify Renal diagnose Renal monitor disease monitor response to assess changes in function that may impact on therapy ( , chemotherapy).Dr. Khalid Al-Ani2 Renal Anatomy and Physiologyupair of fist-sized organs located on either side of the spinal column just behind the lower abdomen (L 1-3) Renal Anatomy and PhysiologyuConsists of Renal cortex and Renal functional unit of the kidney is the nephron; u106nephrons the bladderCortexMedullaCapsuleRenal arteryGlomerulusBowman s capsuleProximal tubuleDistal tubuleCollecting ductHenle sLoopAfferent arterioleDr.

2 Khalid Al-AniBlood is separated from the lumen of the nephron by three layers, 3-Capillary endothelial -basement membrane -epithelial cellDr. Khalid Al-AniThe glomerular filtrate is an ultra filtrate of plasma, that has similar composition of plasma, except for proteinsurineendothelium is impermeable to blood cells as well as large proteins. Proteins with MWtlower than that of albumin (68 KDa) are gets filtered in the glomerulus?uFreely filtered H2O Na+, K+, Cl-, HCO3-, Ca++, Mg+, PO4, etc. Glucose Urea Creatinine InsulinuNone filtered Proteins >68 KDa Immunoglobulins Ferritin Blood CellsDr. Khalid Al-Ani4 The filtration is passive process. The filtration rate of the kidneys depend on the difference between blood pressurein the glomerular capillary and the hydrostatic pressurein the lumen of the nephron GFR= 110 ml/minKidneys receive 2,000 L/ day(25% of cardiac output)200 LitersOf plasma ultra filtrate formed per day2 litersReabsorption from glomerular filtrate% (or negative)Reabsorptioncan be active or passive, and occurs in virtually all segments of the nephronNephrone performed three Functions .

3 Filtration 2. Tubular secretion 3. Tubular reabsorption5 Biochemical Tests of Renal FunctionDiseases affecting kidneys can be selectively damage glomerular or tubular function urineBiochemical Tests of Renal FunctionuTest of glomerular functionMeasurement of GFR Clearance tests Plasma creatinine Blood ureauTubular function testsuUrinalysisDr. Khalid Al-AniMeasurement of Glomerular Filtration Rate (GFR)reflects no of functional nephronesMeasurement of Glomerular Filtration Rate (GFR)uMeasurement is based on concept of clearance: - Measuring urinary excretion of a substance (X) that is completely filtered from the blood by the of Glomerular Filtration Rate (GFR)-contiuIf clearance = GFR then substance xproperties: - freely filtered by glomeruli Not secreted or reabsorbed or metabolized by tubular cells Non-toxic and easily measurableDr.

4 Khalid Al-AniDetermination of ClearanceuClearance = (U x V)/PWhere Uis the urinary concentration of substance xVis the rate of urine formation (mL/min)Pis the plasma concentration of substance xInulin ClearanceuGold StandarduPlant polysaccharideumeasurement of inulin clearence requires the infusion of inulin into blooduclinically is not suitableCreatinine ClearanceuCreatineis a nitrogen containing compounduformed from glycine, arginine, methioninein the liver7 Creatinine Clearance contistored in muscle as creatinephosphate Dr. Khalid Al-AniCreatinine Clearance of muscle creatine converted to creatinine (Cr) each dayuAmount of Cr produced relates to muscle massuFreely filtered at the glomerulusuCreatinine clearence =110ml/minuCorrected to standard body surface area of active tubular excretion(10%).

5 UThis is of little significant for normal GFRuWhen GFR< 10 ml/min, GFR is over estimated8 Creatinine Clearance:advantage and disadvantageuTimed urine collection for creatinine measurement (usually 24h)Problems: -uPractical problems of accurate urine collection and volume consuming, inconvenient and potentially unreliable uCarried out for transplanted kidneys & degree of Renal impairmentPlasma Creatinine ConcentrationuMost reliable simple biochemical test of GFRuplasma Cr level remains fairly constant through adult lifePlasma Creatinine Concentration Cr can increase by 30% 7 hrsafter level can be changed independently to Renal diseasedecreased in-starvation -wasting disease -pregnancy-immediately after surgery-steroid therapyPlasma Creatinine Concentration contiDr.

6 Khalid Al-Ani9uCr Normal reference value 60-120 mole/lOr mg/dluConcentration inversely related to Creatinine Concentration contiPlasma Creatinine Concentration Cr level can be misleading uGFR can decrease by 50% before plasma Cr rise beyond normal rangeuNormal Cr level does not imply normal Renal functionPlasma Creatinine Concentration Urea uUrea is nitrogen containing compound formed in the liver as the end product of protein metabolism and digestion. ueliminate in urine as a major nitrogen waste product (85%)10 UREA filtered but about 50%reabsorbed by through passive diffusionutubular reabsorptionincreases at low rate of urine flowuoften used an index of Renal function along with plasma CrDr.

7 Khalid Al-AniBlood UreauBlood Urealevel can be changed independently to Renal diseasehigh protein intake GIT hemorrhagehypovolumia, burns dehydration congestive heart failure Catabolic stateBlood Ureaublood Urea level reduced in starvation Low protein dietSever liver disease uThus, BU needs to be compared to crto determine true Renal dysfunctionuThe levels of urea and Cr almost always are paralleled to each otherHigh plasma Urea(Uremia or Azotemia) (azotemia = elevated BU)The causes can be subdivided toPrerenalRenalintrinsic Renal diseasePostrenalobstruction to urine outflow11 Other Methods for Assessing GFRu51Cr-EDTA, 99Tc-DTPA Exogenous need to be administered Not readily available RadioactiveOther Methods for Assessing inhibitor (MW13 kDa)ufreely filtered at glomerulusuReabsorbed and degraded by proximal tubuleuPlasma concentration reflects GFRuConstant production rate by all nucleated cellsuNo known extra- Renal excretion routesuNot influenced by muscle mass, diet or subjects sex 2-Microglobulin (BMG)uSmall protein (MW= )

8 Unot affected by muscle mass or dietuBMG is filtered in the glomerulus, but is reabsorbed in the Renal tubules. Urinary BMG levels are a sensitive measure of Renal tubular functionuIncreased in Renal failureTests of Tubular Functionperformed less frequentlyuProximal Tubular Function Aminoaciduria Glycosuria with normal blood glucoseuDistal Tubular FunctionDr. Khalid Al-Ani12 Urinalysis (UA)General urine examination (GUE)uit is a general test for evaluation of Renal functionuFresh sample = Valid sampleuPhysical, uchemical and umacroscopic examinationUrinalysis (UA)-contiPhysical examination includesuAppearanceColour, turbidityupHuSpecific gravity and osmolalityuMicroscopic examination includesSediments RBCS WBC CrystalsUrinalysis (UA)Appearance clearqTurbidity:(infection, nephrotic syndrome, proteinuria)qColour:amber lightColoured-haemoglobin, myoglobin, Jaundice, drugs, beet13 Urine pHuNormally acidicNormal that is >8 or less <4 is physiological impossible.

9 In general urine parallels serum pHDr. Khalid Al-AniUrine OsmolalityuNormal Average: 400-900 mOsm/kg H2 OMax 1200 mOsm/kgPurpose= Assess the ability of kidneys to dilute or concentrate urine-tubular functionUrine valuesdehydrationdiabetes mellitushyperglycemiahypernatremiauDecre ased valuesoverhydrationhyponatremia diabetes insipidus Specific measure of the DENSITY of urinecompared with the density of higher the number=the more concentrated the urine. 14 Specific Gravity-contiuIncreased Specific GravityuLacking fluids uIncreased ADH uFalsely high= glucose, protein, or dye in urineuDecreased Specific GravityuDilute urine uDecreased ADH (diabetes insipidus)Dr.

10 Khalid Al-AniUrinalysis (UA)Chemical examination includesuProteinuGlucoseuKetone bodiesuBilirubinuBlooduNitritesUrine proteinNormal value up to 150mg/dayq(30% albumin, 30% globulins and 40% Tamm-Horsfall)qNormally, Urine sticks -veqUrine sticks +ve= >300mg/LUrine proteinProteinuriauoverflow (raised plasma Low MW Proteins, BenceJones, myoglobin)uRenal diseases 15 Urine glucoseuNormally veu+veurine glucose Increased blood glucose Low Renal threshold or other tubular disordersuFalse +ve Ascorbic aciduKetone bodies Veubilirubin veuNitrite Ve, +veduring UTI by gram +vebacteriaDr. Khalid Al-AniMicroscopic examinationUrine sedimentFreshly passed urine. looking forqCells, qCasts (Tamm-Horsfallprotein)qCrystalsMicroscop ic examination Urine sediment-contCellsqRBCSqWBC qepithelial 16 WBC 0-1 HPF The presence of more than 5 WBC's/ hpfmay suggest -infection, pyelonephritis or inflammation of the genitourinary tract RBCS 0-1 HPF Large no.