1、Unit Eight Formation and Excretion of UrineDepartment of Physiology,Zhengzhou UniversityZhao WenchaoKidneys1.Produce urine2.Endocrine functionRenin,EPO3.Promote transformation of 25-OH-VitD3 to 1,25-(OH)2-VitD3 4.Glyconeogenesis1.Produce urine(1).Eliminate waste products of metabolism,foreign compou
2、nds,excess substances(2).Involvement in water and electrolytes balances1.Functional anatomy of kidneys2.Formation of urine3.Several techniques in renal research4.Micturition reflex5.Regulation of urine production1.Functional anatomy of kidneysNephronCollecting ductJuxtaglomerular apparatusCapillarie
3、sBlood supply of kidneysNephronRenal corpuscleRenal tubuleGlomerulusBowmans capsuleRenal tubuleProximal tubuleThin segments of loop of HenleDistal tubuleProximal convoluted tubule Thick segment of descending limbThin segment of descending limbThin segment of ascending limbDistal convoluted tubule Th
4、ick segment of ascending limbCortical nephronMedullary nephronQuantitySmallDiameter of ateriole:Afferent EfferentLargeAfferent=EfferentLoop of HenleShortLongCapillaries derived from efferent ateriolePeritubular capillariesPeritubular capillaries and vasa rectaFormation of urine1.Functional anatomy o
5、f kidneysNephronCollecting ductJuxtaglomerular apparatusCapillariesBlood supply of kidneysJuxtaglomerular apparatusJuxtaglomerular cellsExtraglomerular mesangial cellsMacula densaSecretion of reninSense NaCl level in tubular fluid and regulate secretion of renin1.Functional anatomy of kidneysNephron
6、Collecting ductJuxtaglomerular apparatusCapillariesBlood supply of kidneysBlood supply of kidneys(1)Large blood flow,94%in cortex and 6%in medulla(2)Two sets of capillaries(3)High pressure in glomerular capillaries(4)Low pressure in peritubular capillaries(5)U-shape vasa recta(6)Autoregulation,sympa
7、thetic and humoral regulationAVBP BP increaseincreaseMyogenicMyogenic activity increaseactivity increaseIncrease Increase resistanceresistance80-160 mmHg1.Functional anatomy of kidneys2.Formation of urine3.Several techniques in renal research4.Micturition reflex5.Regulation of urine production2.Form
8、ation of urine2.1 Glomerular filtration2.2 Reabsorption in renal tubule and collecting duct2.3 Secretion by renal tubule and collecting duct2.4 Mechanisms of concentrated and diluted urine 2.1 Glomerular filtrationUltrafiltrationFiltration membraneEndothelial cellBasement membraneFoot process of pod
9、ocyteFenestration:70-90nm2-8 nmFiltration slit,coated with filtration slit membrane including small slitsUltrafiltrateProteins with negative chargeMechanical barrierCharge barrierUltrafiltrate:lack of proteins and blood cellsGlomerular filtration rate(GFR):125ml/minRenal plasma flow:660ml/minFiltrat
10、ion fraction(19%)Blood pressure in glomerulus(PGC)Colloid osmotic pressure in ultrafiltrate(p pT)Colloid osmotic pressure in glomerulus(p pGC)Hydrostatic pressure in Bowmans capsule(PT)(PGC+p pT)(PT+p pGC)=effective filtration pressure(EFP)(45+0 0)(10+2525)=10mmHgFiltration equilibriumIncrease in re
11、nal plasma flow?Characteristics of glomerular filtrationHigh blood pressure in capillariesLow permeability to proteinsGradual increase in colloid osmotic pressure in plasmaHigh hydrostatic pressure in Bowmans capsuleFactors affecting glomerular filtration(1)Blood pressure in glomerulusArterial blood
12、 pressureAfferent and efferent arteriole(2)Colloid osmotic pressure in plasma(3)Pressure in Bowmans capsule(4)Renal plasma flowFiltration equilibriumIncrease in renal plasma flow?(2)Colloid osmotic pressure in plasma(3)Pressure in Bowmans capsule(4)Renal plasma flow(5)Filtration coefficientEffective
13、 permeability coefficientSurface areaRegulation of glomerular filtration(1)Autoregulation(2)Neuroregulation(3)Humoral regulation(1)AutoregulationMyogenic autoregulationTubuloglomerular feedbackTubuloglomerular feedbackRenal blood flow or GFRTubular fluid passing through macula densa(1)Vasoconstricti
14、on of afferent and efferent arteriolesglomerulus(2)Decrease of surface area of filtration membrane(2)NeuroregulationRenal sympathetic nerveNE,a a receptorBlood loss(3)Humoral regulationreninangiotensinogenangiotensin angiotensin angiotensin Renin-angiotensin system(RAS)angiotensin uConstrict afferen
15、t and efferent arteriolesuAfferent arteriole efferent arterioleLow concentrationHigh concentrationangiotensin Low concentrationu Mainly constrict efferent arterioleu Renal blood flow decreaseu Glomerular pressure increaseangiotensin High concentrationuConstrict afferent and efferent arteriolesBlood
16、loss2.Formation of urine2.1 Glomerular filtration2.2 Reabsorption in renal tubule and collecting duct2.3 Secretion by renal tubule and collecting duct2.4 Mechanisms of concentrated and diluted urine 2.2 Reabsorption in renal tubule and collecting ductTranscellular pathwayParacellular pathwayNa+and C
17、l-H2O HCO3-K+GlucoseCa2+Na+and Cl-Proximal tubuleLoop of HenleDistal tubuleCollecting ductFiltration:500g Na+,Urine:3-5gNa+and Cl-Proximal tubuleFirst halfSecond halfFirst half of proximal tubule65%Fail to reabsorb Cl-Apical Basolateral First half of proximal tubuleNa pumpNa+Na+-glucose cotransporte
18、rNa+-amino acid cotransporterNa+-H+exchangerOsmotic pressure H2O Promote reabsorption by capillaries Cl-Cl-Second half of proximal tubuleTranscellular pathwayParacellular pathwayApical Basolateral Na pumpNa+Na+-H+exchangerNa+H+Cl-HCO3-Cl-HCO3-exchanger+CO2K+K+-Cl-cotransporterCl-Na+Na+and Cl-Proxima
19、l tubuleLoop of HenleDistal tubuleCollecting ductNa+and Cl-Loop of HenleThick segment of descending limbThin segment of descending limbThin segment of ascending limbThick segment of ascending limbPermeable to H2O but not NaClPermeable to NaCl but not H2OImpermeable to H2OThick segment of ascending l
20、imbApical Basolateral Na pumpNa+Na+K+2Cl-Na+-K+-2Cl-cotransporterCl-channelK+channelNa+Ca2+K+Impermeable to H2ONa+and Cl-Distal tubuleCollecting ductFirst halfSecond halfPrinciple cellIntercalated cellApical Basolateral Na pumpNa+Na+Cl-Na+-Cl-cotransporterNa+channelNa+Cl-Cl-channelH2O Proximal tubul
21、e:65%Osmotic pressureTranscellular pathwayParacellular pathwayApical Basolateral AquaporinRegulation by vasopressin in distal tubule and collecting ductProximal tubule:85%Thick segment of ascending limbLoop of Henle:Distal tubule and collecting ductHCO3-HCO3-Proximal tubule:85%Apical Basolateral Na
22、pumpNa+Na+-H+exchangerNa+H+HCO3-+CO2CO2+H2OHCO3-CACAThick segment of ascending limbLoop of Henle:Distal tubule and collecting duct:proton pumpReabsorption of HCO3-:keep acid-base balance K+Proximal tubule:65%Thick segment of ascending limbLoop of Henle:Distal tubule and collecting duct:K+secretionGl
23、ucoseOnly in Proximal tubuleApical Basolateral Na+-dependent glucose transporter(SGLT)Glucose transporter 2Renal threshold for glucoseDifferent in different nephronsMaximal rate of transport of glucose(Tm-G)250500200400Glucose(mg/min)Plasma glucose(mg/ml)Ca2+Proximal tubule:70%Thick segment of ascen
24、ding limbLoop of HenleDistal tubule and collecting ductApical Basolateral Ca2+Proximal tubule:70%Transcellular pathwayParacellular pathway80%Solvent drag(溶剂拖曳溶剂拖曳)20%Ca2+Na+Ca2+pumpNa+-Ca2+exchangerCa2+channelCa2+Factors affecting Ca2+reabsorption(1)Parathyroid hormone,PTH(2)Vitmin D3(3)Ca2+level in
25、 plasma(4)Extracellular fluid(5)pH of body fluidSolvent drag(溶剂拖曳溶剂拖曳)SummaryNa+and Cl-H2O HCO3-K+GlucoseCa2+Proximal tubuleLoop of HenleDistal tubule and collecting ductProximal tubuleProximal tubuleProximal tubuleRegulation of reabsorption(1)Constant fractional reabsorption(2)Osmotic diuresis Reab
26、sorptionGFRGlomerulotubular balance65-70%2.Formation of urine2.1 Glomerular filtration2.2 Reabsorption in renal tubule and collecting duct2.3 Secretion by renal tubule and collecting duct2.4 Mechanisms of concentrated and diluted urine 2.3 Secretion by renal tubule and collecting ductH+K+NH3H+Proxim
27、al tubuleDistal tubule and collecting ductNa+-H+exchangerProton pumpProton pumpH+-K+ATPaseNa+-H+exchangerFactors affecting H+secretion(1)pH in body(2)K+level in plasmaApical Basolateral Na+-H+exchangerH+Na+Na+-K+exchangerK+Na+NH3Proximal tubuleCollecting ductGlutamine2NH4+2HCO3-NH3+H+NH3Proximal tub
28、uleApical Basolateral NH4+HCO3-NH3+H+Na+-H+exchangerH+Na+NH4+NH3Collecting ductApical Basolateral NH4+HCO3-NH3+H+Na+-H+exchangerH+Na+NH4+NH4+NH3+H+Regulation of acid-base balance by renal tubule and collecting duct(1)Secretion of H+(2)Reabsorption of HCO3-(3)Secretion of NH3Promote secretion of H+Pr
29、oduction of HCO3-AcidosisK+Distal tubuleCollecting ductApical Basolateral Na+pumpNa+K+K+K+Na+channelNa+Factors affecting K+secretion(1)Tubular flow rate(2)Cl-level in tubular fluidApical Basolateral K+Cl-K+-Cl-cotransporterFactors affecting K+secretion(1)Tubular flow rate(2)Cl-level in tubular fluid
30、(3)AldosteronApical Basolateral Na+pumpNa+K+Na+channelNa+Increase the amount of Na+channelIncrease the production of ATPIncrease the activity of Na+pumpFactors affecting K+secretion(1)Tubular flow rate(2)Cl-level in tubular fluid(3)AldosteronApical Basolateral Na+pumpNa+K+Na+channelNa+(4)Intake of K
31、+Increase the amount of K+channelIncrease production of aldosteronIncrease the activity of Na+pump2.Formation of urine2.1 Glomerular filtration2.2 Reabsorption in renal tubule and collecting duct2.3 Secretion by renal tubule and collecting duct2.4 Mechanisms of concentrated and diluted urine 2.4 Mec
32、hanisms of concentrated and diluted urine Hyperosmotic renal medulla Permeability of collecting duct to water How hyperosmotic pressure is produced?Vasopressin CortexOuter medullaInner medullaOuter medullaThick segment of ascending limbActive transport of NaCl and is not premeable to H2OThick segmen
33、t of ascending limb:HypoosmoticOuter medulla limb:HyperosmoticCortexOuter medullaInner medullaInner medullaNaCl and UreaNaCl:Thin segment of descending limbThin segment of ascending limbPermeable to H2O but not NaClPermeable to NaCl but not H2OInner medullaNaCl and UreaUrea:Thin segment of ascending
34、 limbDistal convoluted tubule,cortical and outer medullary collecting ductPermeable to ureaImpermeable to urea with active transport of NaClInner medullary collecting ductPermeable to ureaCortexOuter medullaInner medullaUrea recyclingInner medullaNaCl and UreaOuter medullaNaClCapillaries in inner me
35、dulla take away NaCl and urea?U-shape vasa rectaPermeable to H2O and solutesDistal convoluted tubule and collecting ductPermeability to H2O is regulated by vasopressinIn the presence of vasopressinIn the absence of vasopressinPermeability to H2OPermeable to H2OImpermeable to H2OCortexOuter medullaIn
36、ner medullaIn the presence of vasopressin:Permeable to H2Oconcentrated ureaIn the absence of vasopressin:impermeable to H2O Active transport of NaClDiluted urea1.Functional anatomy of kidneys2.Formation of urine3.Several techniques in renal research4.Micturition reflex5.Regulation of urine productio
37、n3.Several techniques in renal researchRenal plasma flow:660ml/minGFR:125ml/minClearanceCxLevel in plasmaPxLevel in urineUxUrine volume VCxUxVPxMeasurement renal plasma flow(RPF)UxVCxPxUxVRPFPxRPFUxVPxRPFUxVPxPAH and diodrast:90%Measurement renal plasma flow(RPF)RPFUxVPx0.9RPFUxVPx0.9Renal blood flo
38、wMeasurement of GFRUxVInulinFiltrated by glomerulussecretion Reabsorption GFRPxRx Sx 0 0 UxVGFRPxGFRUxVPxFiltration fractionPresumption of functions of renal tubule and collecting ductIn the presence of reabsorptionClearance GFR 1.Functional anatomy of kidneys2.Formation of urine3.Several techniques
39、 in renal research4.Micturition reflex5.Regulation of urine production4.Micturition reflexDetrusor muscleInternal urethral muscleExternal urethral muscleReceptors in bladderReceptors in posterior urethraSympathetic and pelvic nervePudendal vervePelvic nerve BladderNo urine0Pressure30-50ml5-10cm of w
40、ater200-300mlIncrease slightlyStress relaxation300-400mlIncrease significantlyMicturition reflexReceptors in bladderActivationPelvic nerve Micturition center in sacral segments of cordMicturition center in cerebral cortex and brain stemPelvic nerve Contraction of detrusor muscleRelaxation of interna
41、l urethral muscleUrine enter posterior urethraRelaxation of external urethral muscle1.Functional anatomy of kidneys2.Formation of urine3.Several techniques in renal research4.Micturition reflex5.Regulation of urine production5.Regulation of urine production5.1 Neuroregulation5.2 Humoral regulation5.
42、1 NeuroregulationRenal sympathetic nerve1.Decrease renal blood flow2.Increase the production of reninAngiotensin Aldosterone3.Promote reabsorption of Na+,Cl-and H2O5.2 Humoral regulationreninangiotensinogenangiotensin angiotensin angiotensin VasopressinVasopressinVasopressinV1 receptor in blood vess
43、elsV2 receptor distal tubule and collecting ductBPActivation of adenyl cyclasecAMPActivation of PKAAquaporinApical Basolateral Regulation of vasopressin(1)Osmotic pressure of extracellular fluidOsmoreceptorVasopressinIntake of too much waterVasopressinUrine volumeWater diuresisBlood volume(2)Blood p
44、ressureCardiopulmonary receptorVasopressinBaroreceptorVasopressinreninangiotensinogenangiotensin angiotensin angiotensin Aldosterone(1)angiotensin Promote Na+reabsorption in proximal tubule(2)Aldosterone Increase the amount of Na+channelIncrease the production of ATPIncrease the activity of Na+pump(
45、3)Regulation of reninuRenal mechanismsuNeural mechanismuHumoral mechanismStretch receptor in afferent arterioleMacula densaBlood volumeReninTubular Na+level Renal sympathetic nerveE,NECirculatory blood volumeRenal sympathetic nerveCardiopulmonary receptorVasopressinBaroreceptorReninRenal bloodNa+reabsorptionStretch receptor in afferent arterioleMacula densaE,NEangiotensin Aldosterone
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