1、Unit Eight Formation and Excretion of Urine,Department of Physiology, Zhengzhou University Zhao Wenchao,Kidneys,1. Produce urine,2. Endocrine function,Renin，EPO,3. Promote transformation of 25-OH-VitD3 to 1，25-(OH)2-VitD3,4. Glyconeogenesis,1. Produce urine,(1). Eliminate waste products of metabolis
2、m, foreign compounds, excess substances,(2). Involvement in water and electrolytes balances,1. Functional anatomy of kidneys,2. Formation of urine,3. Several techniques in renal research,4. Micturition reflex,5. Regulation of urine production,1. Functional anatomy of kidneys,Nephron,Collecting duct,
3、Juxtaglomerular apparatus,Capillaries,Blood supply of kidneys,Nephron,Renal corpuscle,Renal tubule,Glomerulus,Bowmans capsule,Renal tubule,Proximal tubule,Thin segments of loop of Henle,Distal tubule,Proximal convoluted tubule,Thick segment of descending limb,Thin segment of descending limb,Thin seg
4、ment of ascending limb,Distal convoluted tubule,Thick segment of ascending limb,Cortical nephron,Medullary nephron,Quantity,Small,Diameter of ateriole :,Afferent Efferent,Large,Afferent = Efferent,Loop of Henle,Short,Long,Capillaries derived from efferent ateriole,Peritubular capillaries,Peritubular
5、 capillaries and vasa recta,Formation of urine,1. Functional anatomy of kidneys,Nephron,Collecting duct,Juxtaglomerular apparatus,Capillaries,Blood supply of kidneys,Juxtaglomerular apparatus,Juxtaglomerular cells,Extraglomerular mesangial cells,Macula densa,Secretion of renin,Sense NaCl level in tu
6、bular fluid and regulate secretion of renin,1. Functional anatomy of kidneys,Nephron,Collecting duct,Juxtaglomerular apparatus,Capillaries,Blood supply of kidneys,Blood supply of kidneys,(1) Large blood flow, 94% in cortex and 6% in medulla,(2) Two sets of capillaries,(3) High pressure in glomerular
7、 capillaries,(4) Low pressure in peritubular capillaries,(5) U-shape vasa recta,(6) Autoregulation, sympathetic and humoral regulation,BP increase,Myogenic activity increase,Increase resistance,80-160 mmHg,1. Functional anatomy of kidneys,2. Formation of urine,3. Several techniques in renal research
8、,4. Micturition reflex,5. Regulation of urine production,2. Formation of urine,2.1 Glomerular filtration,2.2 Reabsorption in renal tubule and collecting duct,2.3 Secretion by renal tubule and collecting duct,2.4 Mechanisms of concentrated and diluted urine,2.1 Glomerular filtration,Ultrafiltration,F
9、iltration membrane,Endothelial cell,Basement membrane,Foot process of podocyte,Fenestration: 70-90nm,2-8 nm,Filtration slit, coated with filtration slit membrane including small slits,Ultrafiltrate,Proteins with negative charge,Mechanical barrier,Charge barrier,Ultrafiltrate: lack of proteins and bl
10、ood cells,Glomerular filtration rate (GFR): 125ml/min,Renal plasma flow: 660ml/min,Filtration fraction(19%),Blood pressure in glomerulus(PGC),Colloid osmotic pressure in ultrafiltrate(pT),Colloid osmotic pressure in glomerulus(pGC),Hydrostatic pressure in Bowmans capsule(PT),( PGC + pT) ( PT+pGC ) =
11、 effective filtration pressure (EFP),( 45 + 0) ( 10+25 ) = 10mmHg,Filtration equilibrium,Increase in renal plasma flow ?,Characteristics of glomerular filtration,High blood pressure in capillaries,Low permeability to proteins,Gradual increase in colloid osmotic pressure in plasma,High hydrostatic pr
12、essure in Bowmans capsule,Factors affecting glomerular filtration,(1) Blood pressure in glomerulus,Arterial blood pressure,Afferent and efferent arteriole,(2) Colloid osmotic pressure in plasma,(3) Pressure in Bowmans capsule,(4) Renal plasma flow,Filtration equilibrium,Increase in renal plasma flow
13、 ?,(2) Colloid osmotic pressure in plasma,(3) Pressure in Bowmans capsule,(4) Renal plasma flow,(5) Filtration coefficient,Effective permeability coefficient,Surface area,Regulation of glomerular filtration,(1) Autoregulation,(2) Neuroregulation,(3) Humoral regulation,(1) Autoregulation,Myogenic aut
14、oregulation,Tubuloglomerular feedback,Tubuloglomerular feedback,Renal blood flow or GFR,Tubular fluid passing through macula densa,(1) Vasoconstriction of afferent and efferent arterioles,glomerulus,(2) Decrease of surface area of filtration membrane,(2) Neuroregulation,Renal sympathetic nerve,NE, a
15、 receptor,Blood loss,(3) Humoral regulation,renin,angiotensinogen,angiotensin ,angiotensin ,angiotensin ,Renin - angiotensin system (RAS),angiotensin ,Constrict afferent and efferent arterioles,Afferent arteriole efferent arteriole,Low concentration,High concentration,angiotensin ,Low concentration,
16、Mainly constrict efferent arteriole,Renal blood flow decrease,Glomerular pressure increase,angiotensin ,High concentration,Constrict afferent and efferent arterioles,Blood loss,2. Formation of urine,2.1 Glomerular filtration,2.2 Reabsorption in renal tubule and collecting duct,2.3 Secretion by renal
17、 tubule and collecting duct,2.4 Mechanisms of concentrated and diluted urine,2.2 Reabsorption in renal tubule and collecting duct,Transcellular pathway,Paracellular pathway,Na+ and Cl-,H2O,HCO3-,K+,Glucose,Ca2+,Na+ and Cl-,Proximal tubule,Loop of Henle,Distal tubule,Collecting duct,Filtration: 500g
18、Na+，Urine: 3-5g,Na+ and Cl-,Proximal tubule,First half,Second half,First half of proximal tubule,65%,Fail to reabsorb Cl-,Apical,Basolateral,First half of proximal tubule,Na pump,Na+,Na+-glucose cotransporter,Na+-amino acid cotransporter,Na+-H+ exchanger,Osmotic pressure,H2O,Promote reabsorption by
19、capillaries,Cl-,Cl-,Second half of proximal tubule,Transcellular pathway,Paracellular pathway,Apical,Basolateral,Na pump,Na+,Na+-H+ exchanger,Na+,H+,Cl-,HCO3-,Cl- - HCO3- exchanger,+,CO2,K+,K+-Cl- cotransporter,Cl-,Na+,Na+ and Cl-,Proximal tubule,Loop of Henle,Distal tubule,Collecting duct,Na+ and C
20、l-,Loop of Henle,Thick segment of descending limb,Thin segment of descending limb,Thin segment of ascending limb,Thick segment of ascending limb,Permeable to H2O but not NaCl,Permeable to NaCl but not H2O,Impermeable to H2O,Thick segment of ascending limb,Apical,Basolateral,Na pump,Na+,Na+,K+,2Cl-,N
21、a+-K+-2Cl- cotransporter,Cl- channel,K+ channel,Na+,Ca2+,K+,Impermeable to H2O,Na+ and Cl-,Distal tubule,Collecting duct,First half,Second half,Principle cell,Intercalated cell,Apical,Basolateral,Na pump,Na+,Na+,Cl-,Na+-Cl- cotransporter,Na+ channel,Na+,Cl-,Cl- channel,H2O,Proximal tubule: 65%,Osmot
22、ic pressure,Transcellular pathway,Paracellular pathway,Apical,Basolateral,Aquaporin,Regulation by vasopressin in distal tubule and collecting duct,Proximal tubule: 85%,Thick segment of ascending limb,Loop of Henle:,Distal tubule and collecting duct,HCO3-,HCO3-,Proximal tubule: 85%,Apical,Basolateral
23、,Na pump,Na+,Na+-H+ exchanger,Na+,H+,HCO3-,+,CO2,CO2,+,H2O,HCO3-,CA,CA,Thick segment of ascending limb,Loop of Henle:,Distal tubule and collecting duct: proton pump,Reabsorption of HCO3-: keep acid-base balance,K+,Proximal tubule: 65%,Thick segment of ascending limb,Loop of Henle:,Distal tubule and
24、collecting duct: K+ secretion,Glucose,Only in Proximal tubule,Apical,Basolateral,Na+-dependent glucose transporter(SGLT),Glucose transporter 2,Renal threshold for glucose,Different in different nephrons,Maximal rate of transport of glucose (Tm-G),250,500,200,400,Glucose(mg/min),Plasma glucose(mg/ml)
25、,Ca2+,Proximal tubule: 70%,Thick segment of ascending limb,Loop of Henle,Distal tubule and collecting duct,Apical,Basolateral,Ca2+,Proximal tubule: 70%,Transcellular pathway,Paracellular pathway,80%,Solvent drag(溶剂拖曳),20%,Ca2+,Na+,Ca2+ pump,Na+-Ca2+ exchanger,Ca2+ channel,Ca2+,Factors affecting Ca2+
26、 reabsorption,(1) Parathyroid hormone, PTH,(2) Vitmin D3,(3) Ca2+ level in plasma,(4) Extracellular fluid,(5) pH of body fluid,Solvent drag(溶剂拖曳),Summary,Na+ and Cl-,H2O,HCO3-,K+,Glucose,Ca2+,Proximal tubule,Loop of Henle,Distal tubule and collecting duct,Proximal tubule,Proximal tubule,Proximal tub
27、ule,Regulation of reabsorption,（1）Constant fractional reabsorption,（2）Osmotic diuresis,Reabsorption,GFR,Glomerulotubular balance,65-70%,2. Formation of urine,2.1 Glomerular filtration,2.2 Reabsorption in renal tubule and collecting duct,2.3 Secretion by renal tubule and collecting duct,2.4 Mechanism
28、s of concentrated and diluted urine,2.3 Secretion by renal tubule and collecting duct,H+,K+,NH3,H+,Proximal tubule,Distal tubule and collecting duct,Na+ - H+ exchanger,Proton pump,Proton pump,H+-K+ ATPase,Na+ - H+ exchanger,Factors affecting H+ secretion,(1) pH in body,(2) K+ level in plasma,Apical,
29、Basolateral,Na+-H+ exchanger,H+,Na+,Na+-K+ exchanger,K+,Na+,NH3,Proximal tubule,Collecting duct,Glutamine,2NH4+,+ 2HCO3-,NH3,+ H+,NH3,Proximal tubule,Apical,Basolateral,NH4+,HCO3-,NH3,+ H+,Na+-H+ exchanger,H+,Na+,NH4+,NH3,Collecting duct,Apical,Basolateral,NH4+,HCO3-,NH3,+ H+,Na+-H+ exchanger,H+,Na+
30、,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 NH3,Promote secretion of H+,Production of HCO3-,Acidosis,K+,Distal tubule,Collecting duct,Apical,Basolateral,Na+ pump,Na+,K+,K+,K+,Na+ channel,Na+,Fa
31、ctors affecting K+ secretion,(1) Tubular flow rate,(2) Cl- level in tubular fluid,Apical,Basolateral,K+,Cl-,K+-Cl- cotransporter,Factors affecting K+ secretion,(1) Tubular flow rate,(2) Cl- level in tubular fluid,(3) Aldosteron,Apical,Basolateral,Na+ pump,Na+,K+,Na+ channel,Na+,Increase the amount o
32、f Na+ channel,Increase the production of ATP,Increase the activity of Na+ pump,Factors affecting K+ secretion,(1) Tubular flow rate,(2) Cl- level in tubular fluid,(3) Aldosteron,Apical,Basolateral,Na+ pump,Na+,K+,Na+ channel,Na+,(4) Intake of K+,Increase the amount of K+ channel,Increase production
33、of aldosteron,Increase the activity of Na+ pump,2. Formation of urine,2.1 Glomerular filtration,2.2 Reabsorption in renal tubule and collecting duct,2.3 Secretion by renal tubule and collecting duct,2.4 Mechanisms of concentrated and diluted urine,2.4 Mechanisms of concentrated and diluted urine,Hyp
34、erosmotic renal medulla,Permeability of collecting duct to water,How hyperosmotic pressure is produced?,Vasopressin,Cortex,Outer medulla,Inner medulla,Outer medulla,Thick segment of ascending limb,Active transport of NaCl and is not premeable to H2O,Thick segment of ascending limb:Hypoosmotic,Outer
35、medulla limb:Hyperosmotic,Cortex,Outer medulla,Inner medulla,Inner medulla,NaCl and Urea,NaCl:,Thin segment of descending limb,Thin segment of ascending limb,Permeable to H2O but not NaCl,Permeable to NaCl but not H2O,Inner medulla,NaCl and Urea,Urea:,Thin segment of ascending limb,Distal convoluted
36、 tubule, cortical and outer medullary collecting duct,Permeable to urea,Impermeable to urea with active transport of NaCl,Inner medullary collecting duct,Permeable to urea,Cortex,Outer medulla,Inner medulla,Urea recycling,Inner medulla,NaCl and Urea,Outer medulla,NaCl,Capillaries in inner medulla ta
37、ke away NaCl and urea?,U-shape vasa recta,Permeable to H2O and solutes,Distal convoluted tubule and collecting duct,Permeability to H2O is regulated by vasopressin,In the presence of vasopressin,In the absence of vasopressin,Permeability to H2O,Permeable to H2O,Impermeable to H2O,Cortex,Outer medull
38、a,Inner medulla,In the presence of vasopressin: Permeable to H2O,concentrated urea,In the absence of vasopressin: impermeable to H2O,Active transport of NaCl,Diluted urea,1. Functional anatomy of kidneys,2. Formation of urine,3. Several techniques in renal research,4. Micturition reflex,5. Regulatio
39、n of urine production,3. Several techniques in renal research,Renal plasma flow: 660ml/min,GFR: 125ml/min,Clearance,Cx,Level in plasma,Px,Level in urine,Ux,Urine volume,V,Cx,Ux,V,Px,Measurement renal plasma flow(RPF),Ux,V,Cx,Px,Ux,V,RPF,Px,RPF,Ux,V,Px,RPF,Ux,V,Px,PAH and diodrast: 90%,Measurement re
40、nal plasma flow(RPF),RPF,Ux,V,Px,0.9,RPF,Ux,V,Px,0.9,Renal blood flow,Measurement of GFR,Ux,V,Inulin,Filtrated by glomerulus,secretion,Reabsorption,GFR,Px,Rx,Sx,0,0,Ux,V,GFR,Px,GFR,Ux,V,Px,Filtration fraction,Presumption of functions of renal tubule and collecting duct,In the presence of reabsorptio
41、n,Clearance,GFR,In the presence of secretion,Clearance,GFR,1. Functional anatomy of kidneys,2. Formation of urine,3. Several techniques in renal research,4. Micturition reflex,5. Regulation of urine production,4. Micturition reflex,Detrusor muscle,Internal urethral muscle,External urethral muscle,Re
42、ceptors in bladder,Receptors in posterior urethra,Sympathetic and pelvic nerve,Pudendal verve,Pelvic nerve,Bladder,No urine,0,Pressure,30-50ml,5-10cm of water,200-300ml,Increase slightly,Stress relaxation,300-400ml,Increase significantly,Micturition reflex,Receptors in bladder,Activation,Pelvic nerv
43、e,Micturition center in sacral segments of cord,Micturition center in cerebral cortex and brain stem,Pelvic nerve,Contraction of detrusor muscle,Relaxation of internal urethral muscle,Urine enter posterior urethra,Relaxation of external urethral muscle,1. Functional anatomy of kidneys,2. Formation o
44、f urine,3. Several techniques in renal research,4. Micturition reflex,5. Regulation of urine production,5. Regulation of urine production,5.1 Neuroregulation,5.2 Humoral regulation,5.1 Neuroregulation,Renal sympathetic nerve,1. Decrease renal blood flow,2. Increase the production of renin,Angiotensi
45、n ,Aldosterone,3. Promote reabsorption of Na+, Cl- and H2O,5.2 Humoral regulation,renin,angiotensinogen,angiotensin ,angiotensin ,angiotensin ,Vasopressin,Vasopressin,Vasopressin,V1 receptor in blood vessels,V2 receptor distal tubule and collecting duct,BP,Activation of adenyl cyclase,cAMP,Activatio
46、n of PKA,Aquaporin,Apical,Basolateral,Regulation of vasopressin,(1) Osmotic pressure of extracellular fluid,Osmoreceptor,Vasopressin,Intake of too much water,Vasopressin,Urine volume,Water diuresis,Blood volume,(2),Blood pressure,Cardiopulmonary receptor,Vasopressin,Baroreceptor,Vasopressin,renin,an
47、giotensinogen,angiotensin ,angiotensin ,angiotensin ,Aldosterone,(1) angiotensin ,Promote Na+ reabsorption in proximal tubule,(2)Aldosterone,Increase the amount of Na+ channel,Increase the production of ATP,Increase the activity of Na+ pump,(3) Regulation of renin,Renal mechanisms,Neural mechanism,H
48、umoral mechanism,Stretch receptor in afferent arteriole,Macula densa,Blood volume,Renin,Tubular Na+ level,Renal sympathetic nerve,E, NE,Circulatory blood volume,Renal sympathetic nerve,Cardiopulmonary receptor,Vasopressin,Baroreceptor,Renin,Renal blood,Na+ reabsorption,Stretch receptor in afferent arteriole,Macula densa,E, NE,angiotensin ,Aldosterone,
