1、Figure 26-3; Guyton and Hall,Nephron: functional unit of the kidney,Figure 26-4; Guyton and Hall,Nephron Tubular Segments,Structure of the juxtaglomerular apparatus: macula densa,Figure 26-17; Guyton and Hall,Cortical and Juxtamedullary Nephron Segments,Figure 26-5; Guyton and Hall,http:/ of Kidney
2、Functions,Excretion of metabolic waste products: urea, creatinine, bilirubin, hydrogenExcretion of foreign chemicals: drugs, toxins, pesticides, food additivesSecretion, metabolism, and excretion of hormones renal erythropoetic factor 1,25 dihydroxycholecalciferol (Vitamin D) ReninRegulation of acid
3、-base balanceGluconeogenesis: glucose synthesis from amino acidsControl of arterial pressureRegulation of water & electrolyte excretion,Basic Mechanisms of Urine Formation,Figure 26-8; Guyton and Hall,Renal Handling of Different Substances,Figure 26-9; Guyton and Hall,Renal Handling of Water and Sol
4、utes,Filtration Reabsorption Excretion,Water (liters/day) 180 179,Sodium (mmol/day) 25,560 25,410,Glucose (gm/day) 180 0,Creatinine (gm/day) 1.8 1.8,1,180,0,150,Glomerular Capillary Filtration Barrier,Figure 26-10; Guyton and Hall,The Ability of a Solute to Penetrate the Glomerular Membrane Depends
5、on:Molecular size ( small molecules filterability) Ionic charge (cations filterability),Effects of Size and Electrical Charge of Dextran on Filterability by Glomerular Capillaries,Figure 26-11; Guyton and Hall,Clinical Significance of Proteinuria,Early detection of renal disease in at-risk patients
6、hypertension: hypertensive renal disease diabetes: diabetic nephropathy pregnancy: gestational proteinuric hypertension (pre-eclampsia) annual “check-up”: renal disease can be silent Assessment and monitoring of known renal disease “Is the dipstick OK?”: dipstick protein tests are not very sensitive
7、 and not accurate: “trace” results can be normal & positives must be confirmed by quantitative laboratory test.,Figure 26-12; Guyton and Hall,Glomerular Hydrostatic Pressure (PG),Is the determinant of GFR most subjectto physiological controlFactors that influence PG arterial pressure (effect is buff
8、ered by autoregulation) afferent arteriolar resistance efferent arteriolar resistance,Figure 26-14; Guyton and Hall,Effect of changes in afferent arteriolar or efferent arteriolar resistance,RE,RBF,G,GFR,_,determined by : FF = GFR / RPF,Kf GFR PB GFR G GFRA GFF G PG GFRRA PGRE PG,Summary of Determin
9、ants of GFR,GFR,GFR,GFR,(as long as RE 3-4 x normal),Assessing Kidney Function,Albumin excretion (microalbuminuria)Plasma concentration of waste products (e.g. BUN, creatinine)Urine specific gravity, urine concentrating abilityImaging methods (e.g. MRI, PET, arteriograms,iv pyelography, ultrasound e
10、tc)Isotope renal scansBiopsyClearance methods (e.g. 24-hr creatinine clearance)etc,Clearance,Clearance is a general concept that describes therate at which substances are removed (cleared)from the plasma.,Clearance Technique,Renal clearance of a substance is the volume of plasma completely cleared o
11、f a substance per min.,Cs x Ps = Us x V,Where: Cs = clearance of substance SPs = plasma conc. of substance SUs = urine conc. of substance SV = urine flow rate,For a substance that is freely filtered, but not reabsorbed or secreted (inulin, 125 I-iothalamate, creatinine), renal clearance is equal to
12、GFR,Use of Clearance to Measure GFR,amount filtered = amount excreted,Copyright 2006 by Elsevier, Inc.,Calculate the GFR from the following data:,Pinulin = 1.0 mg / 100ml Uinulin = 125 mg/100 ml Urine flow rate = 1.0 ml/min,Steady-state relationship between GFR and serum creatinine concentration,Fig
13、ure 27-19; Guyton and Hall,Clearances of Different Substances,Clearance of inulin (Cin) = GFR,if Cx Cin: indicates reabsorption of x,Substance Clearance (ml/min)inulin 125glucose 0sodium 0.9urea 70,Clearance creatinine (Ccreat) 140 (used to estimate GFR),if Cx Cin: indicates secretion of x,1. Sympat
14、hetic Nervous SystemRA + RE GFR + RBF,Control of Glomerular Filtration,3. Angiotensin IIRE GFR + RBF(prevents a decrease in GFR),2. Catecholamines ( norepinephrine)RA + RE GFR + RBF,Control of Glomerular Filtration,5. Endothelial-Derived Nitric Oxide (EDRF)RA + RE GFR + RBF,4. ProstaglandinsRA + RE
15、GFR + RBF,6. EndothelinRA + RE GFR + RBF,Control of Glomerular Filtration,7. Autoregulation of GFR and Renal Blood FlowMyogenic MechanismMacula Densa Feedback (tubuloglomerular feedback) Angiotensin II ( contributes to GFR but not RBF autoregulation),Renal Artery Pressure (mmHg),100,80,Renal BloodFl
16、ow,Glomerular Filtration Rate,Renal Autoregulation,Time (min),0,1,2,3,4,5,120,Copyright 2006 by Elsevier, Inc.,Renal Blood Flow and GFR Autoregulation,Figure 26-16; Guyton and Hall,Macula Densa Feedback,GFR,Distal NaClDelivery,Macula Densa NaCl Reabsorption,Afferent Arteriolar Resistance,GFR (return
17、 toward normal),(macula densa feedback),Myogenic Mechanism,Stretch of Blood Vessel,Cell Ca+ Permeability,Arterial Pressure,Intracell. Ca+,Blood Flow,Vascular Resistance,Regulation of GFR by Ang II,GFR,Efferent Arteriolar,Resistance,Macula,Densa NaCl,Blood,Pressure,Macula densa feedback mechanism for GFR autoregulation,Figure 26-18; Guyton and Hall,
