2012 4-16 renal physiology


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2012 4-16 renal physiology

  1. 1. Renal Physiology Xiaohong Xia 夏晓红 Department of Physiology Hebei Medical UniversityE-mail: xiaunmc@hotmail.com)
  2. 2. About this Chapter• Anatomy of the excretory system• How the kidney is organized• How the nephron works to filter blood, recycle, secrete, and excrete• How filtration is regulated• Urination reflex
  3. 3. Kidney Function1. Regulation of water and inorganic ions balance2. Excretion of metabolic waste products3. Removing of foreign chemicals by producing﹠excreting urine to maintain the internal homeostasis of the body
  4. 4. Kidney Function4. Secretion of hormonesa. Erythropoietin (EPO --- is produced by interstitial cells in peritubular capillary.), which controls erythrocyte productionb. Renin, ( is produced by juxtaglomerular cell) which controls formation of angiotensinc. 1,25-dihydroxyvitamin D3 , which influences calcium balance
  5. 5. Outline:• 􀂋 Functional Anatomy of Kidneys and Renal Circulation• 􀂋 Glomerular Filtration• 􀂋 Tubular Processing of Urine Formation• 􀂋 Urine Concentration and Dilution• 􀂋 Regulation of Water and Sodium Excretion• 􀂋 Renal Clearance• 􀂋 Urine Volume and Micturition
  6. 6. SECTION 1: Functional Anatomy of Kidneys and Renal CirculationUrinary system : paired kidneys paired ureters a bladder a urethra
  7. 7. Anatomical Characteristics of the Kidney The kidney: renal cortex renal medulla renal pelvis
  8. 8. Anatomical Characteristics of the Kidney1. Nephrons: functional unit of kidneys (1). Consist of nephron• Nephron is the basic smallest functional unit of kidney.• Nephron consists of renal corpuscle and renal tubule.• Each kidney is composed of about 1 million microscopic functional unit.
  9. 9. Consist of Nephron glomerulus renal corpuscle Bowman’s capsuleNephron proximal convoluted tubule proximal tubule thick descending limb thin descending limb renal tubule thin segment loop of Henley thin ascending limb thick ascending limb distal tubule distal convoluted tubule
  10. 10. Anatomical Characteristics of the KidneyFunctional unit -nephron: Corpuscle: Bowman’s capsule Glomerulus capillaries Tubule: PCT Loop of Henley DCT Collecting duct
  11. 11. Two Types of Nephron• Cortical nephrons • ~85% of all nephrons • Located in the cortex• Juxtamedullary nephrons • Closer to renal medulla • Loops of Henle extend deep into renal pyramids
  12. 12. Tab. 8-1. Differences between a cortical and a Juxtamedullary nephron Cortical nephron Juxtamedullary nephron Location Outer part of the cortex Inner part of the cortex next to the medulla Glomerulus Small Big Loop of Henle Short, next to outer cortex Longer, into inner part of cortex Diameter of AA* AA > EA AA = EA Diameter of EA** 2 1 EA To form Peritubular capillary To form Vasa recta Sympathetic Rich Poor nerve innervation Concentration of renin High Almost no Ratio 90% 10% Function Reabsorption and secretion Concentrate and dilute urine * AA = afferent glomerular arteriole ** EA = efferent glomerular arteriole
  13. 13. Cortical and Juxtamedullary Nephrons
  14. 14. 2. Collecting ductFunction: As same as distal tubular3. Juxaglomerular apparatus (JGA) macula densa --- in initial portion of DCT Function : sense change of volume and NaCl concentration of tubular fluid , and transfer information to JGC mesangial cell juxtaglomerular cell (JGC) --- in walls of the afferent arterioles) Function: secrete renin
  15. 15. Juxaglomerular apparatusJA locate in cortical nephron, consist of juxtaglomerular cell、 mesangial cell and macula densa.
  16. 16. Tubulo-glomerular Feedback• Macula densa can detects Na+, K+ and Cl- of tubular fluid, and then sent some information to glomerule, regulation releasing of renin and glomerular filtration rate. This process is called Tubulo- glomerullar feedback.
  17. 17. Renal circulation1.Characteristics of renal blood circulation• Huge volumes blood: 1200ml/min,1/5 – 1/4 of the cardiac output.• Distribution: Cortex 94%, outer medulla 5 - 6%, inner medulla <1%.• Two capillary beds: Renal artery→interlobar arteries →arcuate arteries →afferent arterioles →glomerular capillaries →efferent arteriole →peritubular capillaries →arcuate vein →interlobar vein →renal vein.
  18. 18. Renal circulation• Glomerular capillaries: Higher pressure, benefit for filtration• Peritubular capillaries: Lower pressure, benefit for reabsorption• Vasa recta Concentrate and dilute urine
  19. 19. Renal circulation Glomerular Peritubular capillary capillary cortex medulla vasa recta
  20. 20. Regulation of renal blood flow Autoregulation When arterial pressure is in range of 80 to 180 mmHg, renal blood flow (RBF) is relatively constant in denervated, isolated or intact kidney. Flow autoregulation is a major factor that controls RBF Mechanism of autoregulation: myogenic theory of autoregulation Physiological significance: To maintain a relatively constant glomerular filtration rate (GFR).
  21. 21. Autoregulation of renal blood flow
  22. 22. Neural regulationRenal efferent nerve from brain to kidney• Renal sympathetic nerveRenal afferent nerve from kidney to brain• Renal afferent nerve fiber can be stimulated mechanical and chemical factors.renorenal reflex: One side renal efferent nerve activity can effect other side renal nerve activity. Activity of sympathetic nerves is low, but can increase during hemorrhage, stress and exercise.
  23. 23. Hormonal regulationVasoconstriction RBF• Angiotensin II• Epinephrine• NorepinephrineVasodilation RBF• Prostaglandin• nitrous oxide• Bradykinin
  24. 24. Basic processes for urine formationGlomerular filtration:Most substances in blood, except for protein and cells, arefreely filtrated into Bowmans space.Reabsorption:Water and specific solutes are reabsorbed from tubular fluidback into blood (peritubular capillaries).Secretion:Some substances (waste products, etc.) are secreted fromperitubular capillaries or tubular cell interior into tubules. Amount Excreted = Amount filtered – Amount reabsorbed + Amount secreted
  25. 25. Three basic processes of the formation of urine.
  26. 26. Basic processes for urine formation
  27. 27. Section 2 Glomerular FiltrationOnly water and small solutes can be filtrated----selective.
  28. 28. 1. Composition of the glomerular filtratesExcept for proteins, the composition of glomerular filtrates issame as that of plasma. ?
  29. 29. 2. Glomerular filtration membrane The barrier between the capillary blood and the fluid in the Bowman’s space. Composition: three layers• Capillary endothelium --- fenestrations(70-90nm)• Basement membrane --- meshwork• Epithelial cells (podocyte) - --slit pores Figure 26.10a, b
  30. 30. Showing the filtration membran. To be filtered, a substance must passthrough 1. the pores between the endothelial cells of the glomerullar capillary,2. an cellular basement membrane, and 3. the filtration slits between the footprocesses of the podocytes of the inner layer of Bowman’s capsule.
  31. 31. Selective permeability of filtration membrane Structure Characteristics: There are many micropores in each layer Each layer contains negatively charged glycoproteins
  32. 32. Selective permeability of filtration membraneSize selection :impermeable to substanceswith molecule weight (MW)more than 69, 000 or EMR 4.2 nm. (albumin)Charge selection :Repel negative charged substances.
  33. 33. Filtrate Composition• Glomerular filtration barrier restricts the filtration of molecules on the basis of size and electrical charge• Neutral solutes: • Solutes smaller than 180 nanometers in radius are freely filtered • Solutes greater than 360 nanometers do not • Solutes between 180 and 360 nm are filtered to various degrees• Serum albumin is anionic and has a 355 nm radius, only ~7 g is filtered per day (out of ~70 kg/day passing through glomeruli)• In a number of glomerular diseases, the negative charge on various barriers for filtration is lost due to immunologic damage and inflammation, resulting in proteinuria (i.e. increased filtration of serum proteins that are mostly negatively charged).
  34. 34. • Glomerular filtration rate (GFR): The minute volume of plasma filtered through the filtration membrane of the kidneys is called the glomerular filtration rate. (Normally is 125ml/min)• Filtration fraction (FF): The ratio of GFR and renal plasma flow
  35. 35. Factors affecting glomerular filtration• Effective filtration pressure (EFP) The effective filtration pressure of glomerulus represents the sum of the hydrostatic and colloid osmotic forces that either favor or oppose filtration across the glomerular capillaries.• EFP is promotion of filtration.
  36. 36. • Formation and calculate of EPF Formation of EPF depends on three pressures: Glomerular capillary pressure (Pcap) Plasma colloid osmotic pressure (Pcol) Intracapsular pressure (Picap)• Calculate of EPF EFP = Pcap – (Pcol + Picap)• Part of afferent arterial EFP = Pcap – (Pcol + Picap) = 55 – (30 + 15) = 10• Part of efferent arterial EFP = Pcap – (Pcol + Picap) = 55 – (40 + 15) = 0
  37. 37. Effective filtraton pressure
  38. 38. Filtration Coefficient ( Kf )• Filtration coefficient is a minute volume of plasma filtered through the filtration membrane by unit effective filtration pressure drive. Kf =K×S• GFR is dependent on the filtration coefficient as well as on the net filtration pressure. GFR=P× Kf• The surface area the permeability of the glomerular membrane can affect Kf.
  39. 39. Factors Affecting Glomerular FiltrationWhat kind of factors can affect filtration rate? 1.Effective filtration pressure 2.Glomerular capillary pressure 3.Plasma colloid osmotic pressure 4.Intracapsular pressure 5.Renal plasma flow 6.Kf =K×S Kf : filtration coefficient K: permeability coefficient S: surface area the permeability
  40. 40. Regulation of Glomerular Filtration• If the GFR is too high, needed substances cannot be reabsorbed quickly enough and are lost in the urine• If the GFR is too low - everything is reabsorbed, including wastes that are normally disposed of• Control of GFR normally result from adjusting glomerular capillary blood pressure• Three mechanisms control the GFR • Renal autoregulation (intrinsic system) • Neural controls • Hormonal mechanism (the renin-angiotensin system)
  41. 41. Autoregulation of GFR• Under normal conditions (MAP =80-180mmHg) renal autoregulation maintains a nearly constant glomerular filtration rate• Two mechanisms are in operation for autoregulation: • Myogenic mechanism • Tubuloglomerular feedback• Myogenic mechanism: • Arterial pressure rises, afferent arteriole stretches • Vascular smooth muscles contract • Arteriole resistance offsets pressure increase; RBF (& hence GFR) remain constant.• Tubuloglomerular feed back mechanism for autoregulation: • Feedback loop consists of a flow rate (increased NaCl) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA) • Increased GFR (& RBF) triggers release of vasoactive signals • Constricts afferent arteriole leading to a decreased GFR (& RBF)
  42. 42. Extrinsic Controls• When the sympathetic nervous system is at rest: • Renal blood vessels are maximally dilated • Autoregulation mechanisms prevail• Under stress: • Norepinephrine is released by the sympathetic nervous system • Epinephrine is released by the adrenal medulla • Afferent arterioles constrict and filtration is inhibited• The sympathetic nervous system also stimulates the renin-angiotensin mechanism• A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin and erythropoietin
  43. 43. Response to a Reduction in the GFR
  44. 44. Renin-Angiotensin Mechanism• Renin release is triggered by: • Reduced stretch of the granular JG cells • Stimulation of the JG cells by activated macula densa cells • Direct stimulation of the JG cells via 1-adrenergic receptors by renal nerves• Renin acts on angiotensinogen to release angiotensin I which is converted to angiotensin II• Angiotensin II: • Causes mean arterial pressure to rise • Stimulates the adrenal cortex to release aldosterone• As a result, both systemic and glomerular hydrostatic pressure rise
  45. 45. Figure 25.10
  46. 46. Other Factors Affecting Glomerular Filtration• Prostaglandins (PGE2 and PGI2) • Vasodilators produced in response to sympathetic stimulation and angiotensin II • Are thought to prevent renal damage when peripheral resistance is increased• Nitric oxide – vasodilator produced by the vascular endothelium• Adenosine – vasoconstrictor of renal vasculature• Endothelin – a powerful vasoconstrictor secreted by tubule cells
  47. 47. Control of Kf• Mesangial cells have contractile properties, influence capillary filtration by closing some of the capillaries – effects surface area• Podocytes change size of filtration slits
  48. 48. Process of Urine Formation• Glomerular filtration• Tubular reabsorption of the substance from the tubular fluid into blood• Tubular secretion of the substance from the blood into the tubular fluid• Mass Balance • Amount Excreted in Urine = Amount Filtered through glomeruli into renal proximal tubule MINUS amount reabsorbed into capillaries PLUS amount secreted into the tubules
  49. 49. Tubular Secretion• Essentially reabsorption in reverse, where substances move from peritubular capillaries or tubule cells into filtrate• Tubular secretion is important for: • Disposing of substances not already in the filtrate • Eliminating undesirable substances such as urea and uric acid • Ridding the body of excess potassium ions • Controlling blood pH
  50. 50. Tubular reabsorption and secretion
  51. 51. SECTION 3: Tubular processing of urine formation Characteristics and mechanism of reabsorption and secretion Characteristics of reabsorption: quantitatively large More than 99% volume of filtered fluid are reabsorbed (> 178L). selective 100% glucose, 99% sodium and chloride, 85% bicarbonate are reabsorbed Urea and creatinine are partly reabsorbed.
  52. 52. (1). Type of transportation in renal tubule and colllecting duct• Reabsorption and secretion are divided two types• Passive reabsorption (needless energy) Diffusion, osmosis, facilitated diffusion• Active reabsorption (need energy)• Saldium pump (Na+-K+ ATPase), proton pump (H+- ATPase), calcium pump (Ca2+-ATPase).• Cotransport (coupled transport): One transportor can transport two or more substances.• Symport transport: like Na+ and glucose, Na+ and amine acids Antiport transport: like Na+-H+ and Na+-K+• Secondary active transport : like H+ secretion
  53. 53. Na+ active transport in PT epithelium
  54. 54. • Passway of transport Apical membrane, tight juction, brush border, basolateral membrane• Transcellular pathway Na+ apical membrane epithelium Na+ pump peritubular capillary• Paracellular transport Water, Cl- and Na+ tight juction peritubular capillary K+ and Ca2+ are reabsorpted with water by solvent drag
  55. 55. Fig.8-23. The pathway of reabsorption
  56. 56. Reabsorption of transcellular and paracellular pathway
  57. 57. Na+ and Cl - paracellular reabsorption in PT epithelium
  58. 58. Location of reabsorption Proximal tubule Brush border can increase the area of reabsorption Henles loop Distal tubule Collecting duct
  59. 59. (2). Reabsorption and secretion in different part of renal tubule• Proximal tubule (PT) 67% Na+, Cl-, K+ and water; 85% HCO3- and 100% glucose and amine acids are reabsorption secretion H+ 2/3 Transcellular pathway 1/3 Paracellular transport The key of reabsorption is Na+ reabsorption ( the action of Na+ pump in the membrane of proximal tubule).
  60. 60. 1. Na+、Cl- and water reabsorption Na+ and Cl- reabsorption:• About 65 - 70% in proximal tubule, 10% in distal tubule, 20% loop of Henle.• Valume of filtration: 500g/day, Valume of excretion 3 – 5g,99% are reabsorption.• Front part of PT: Na+ reabsorption with HCO3-、 Glucose and Amine acids; Behind part of PT: Na+ reabsorption with Cl-.
  61. 61. • Cl- reabsorption: Passive reabsorption with Na+• water reabsorption: Passive reabsorption with Na+ and Cl-
  62. 62. Na+ transcellular transportation in early part of PT epithelium
  63. 63. Cl- passive reabsorption in later part of PT epithelium
  64. 64. Water passive reabsorption
  65. 65. K+ reabsorption Most of in PT (70%),20% in loop of Henle Active reabsorptionCa2+ reabsorption 70% in PT, 20% in loop of Henle, 9% in DCT 20% is transcellular pathway 80% is paracellular transport
  66. 66. HCO -3 reabsorption and H+ secretion• About 80% in PT, 15% in ascending thick limb, 5% in DCT and CD• H2CO3 CO2 + H2O, CO2 is easy reabsorption• HCO3– reabsorption is priority than Cl-H+ secretion• CO2 + H2O H2CO3 HCO3–+ H+• H+ secretion into lumen
  67. 67. Bicarbonate reabsorption
  68. 68. Glucose and amino acid reabsorptionGlucose reabsorption:99% glucose are reabsorption, no glucose in urine• Location: early part of PT• Type of reabsorption: secondary active transport• Renal glucose threshold When the plasma glucose concentration increases up to a value about 160 to 180 mg per deciliter, glucose can first be detected in the urine, this value is called the renal glucose threshold. 9-10.1 mmol/L (160-180mg/dl)
  69. 69. Glucose secondary active transport in early part of PT
  70. 70. Transport maximum (Tm) 转运极限 Transport maximum is the maximum rate at which the kidney active transport mechanisms can transfer a particular solute into or out of the tubules.Amino acid reabsorption: Location and type of reabsorption as same as glucose
  71. 71. Glucose secondary active transport in early part of PT
  72. 72. Co-transport of amino acids via Na+ symport mechanism.
  73. 73. Loop of Henle:Ascending thick limb of loop of HenleNa+, Cl- and K+ cotransportTransportation rate: Na+ : 2Cl- : K+Distal tubule and collecting duct:Principal cell: Reabsorption Na+ 、water and secretion K+Intercalated cell: Secretion H+
  74. 74. • 12% Na+, Cl- and water are reabsorbed in distal tubule and collecting duct.• Water reabsorption: depends on whether lack of water of body. ADH (discuss later)• Na+ and K+ reabsorption: Aldosteron (discuss later)• K+ secretion: Na+ - K+ - ATPase,• H+ secretion: Na+ -H+ antiport transport• NH3 secretion: Related to H+ secretion NH3 + H+ =NH4+ +NaCl= NH4Cl + Na+ NH4Cl excretion with urine, Na+ reabsorption into blood.
  75. 75. Secretion at the DCT• DCT performs final adjustment of urine• Active secretion or absorption • Absorption of Na+ and Cl- • Secretion of K+ and H+ based on blood pH• Water is regulated by ADH (vasopressin)• Na+, K+ regulated by aldosterone
  76. 76. K+ and H+ secretion in distal tubule and collecting duct
  77. 77. Co-transport of amino acids via Na+ symport mechanism.
  78. 78. Table. 8-2. Summary of transport across PT, DT and collecting duct Proximal tubuleReabsorption Secretion67% of filtered Na+ actively Variable H+ secretion,reabsorbed, not subject to control; depending on acid-baseCl- follows passively. status of body.All filtered glucose and amino acidsreabsorbed by secondary activetransport, not subject to control.65% of filtered H2O osmoticallyreabsorbed, not subject to control.Almost all filtered K+ reabsorbed,not subject to control. Distal tubule and collecting ductReabsorption SecretionVariable Na+ reabsorbed by Variable H+ secretion,Aldosterone; depending on acid-baseCl- follows passively. status of body.Variable H2O reabsorption, Variable K+ secretion,controlled by vasopressin (ADH) controlled by aldosterone.
  79. 79. Urinary Concentration and Dilution• Hypertonic urine: Lack of water in body can forms concentrated urine (1200 mOsm/L).• Hypotonic urine: More water in body can forms dilute urine (50 mOsm/L).• Isotonic urine:Injury of renal function• Urinary dilution: The mechanism for forming a dilute urine is continuously reabsorbing solutes from the distal segments of the tabular system while failing to reabsorb water.• Urinary concentration: The basic requirements for forming a concentrated urine are a high level of ADH and a high osmolarity of the renal medullary interstitial fluid.
  80. 80. formation of dilute and concentrated urine.
  81. 81. Control of Urine Volume and Concentration• Urine volume and osmotic concentration are regulated by controlling water and sodium reabsorption• Precise control allowed via facultative water reabsorption• Osmolality • The number of solute particles dissolved in 1L of water • Reflects the solution’s ability to cause osmosis• Body fluids are measured in milliosmols (mOsm)• The kidneys keep the solute load of body fluids constant at about 300 mOsm• This is accomplished by the countercurrent mechanism
  82. 82.  Formation of concentrated and diluted urine Drink more water ADH water reabsorption in DCT and CD diluted urine. Lack of water ADH water reabsorption in DCT and CD concentrated urine. Role of the vasa recta for maintaining the high solute concentration (NaCl and urea) in the medullary interstitial fluid. Role of countercurrent exchanger
  83. 83. Urinary concentrating environment.
  84. 84. • Basic structure: “U”type of loop of Henle Vasa recta’s cliper type (发卡样排列) Collecting duct from cortex to medulla• Basic function: Different permeability of solutes and water in DCT, CD and loop of Henle.• Osmotic gradient exit from cortex to medulla.
  85. 85. Tab.8-2. Permeabilities of different segments of the renal tubuleSegments of Permeability to Permeability to Permeability torenal tubule water Na+ ureaThick ascending Almost not Active transport of Almost notlimb Na+, Secondary active Transport of Cl-Thin ascending Almost not Yes ModeratelimbThin descending Yes Almost not Almost notlimbDistal convoluted Permeable Secretion of K+ Almost nottubule Under ADH K+-Na+ exchange actionCollecting Permeable Yes Cortex and outerduct Under ADH Medulla almost not action Inner medulla Yes
  86. 86.  Mechanisms for creating osmotic gradient in the medullary interstitial fluid Formation of osmotic gradient is related to physiological characters of each part of renal tubule. Outer medulla: Water are permeated in descending thin limb, but not NaCl and urea. NaCl and urea are permeated in ascending thin limb, but not water. NaCl is active reabsorbed in ascending thick limb, but not Urea and water. Formation of osmotic gradient in outer medulla is due to NaCl active reabsorption in outer medulla.
  87. 87. • Inner medulla:• High concentration urea exit in tubular fluid.• Urea is permeated in CD of inner medulla but not in cortex and outer medulla• NaCl is not permeated in descending thin limb• NaCl is permeated in ascending thin limb• Urea recycling:• Urea is permeated in ascending thin limb, part of urea into ascending thin limb from medulla and then diffusion to interstitial fluid again.• Formation of osmotic gradient in inner medulla is due to urea recycling and NaCl passive diffusion in inner medulla.
  88. 88. Countercurrent Mechanism• Interaction between the flow of filtrate through the loop of Henle (countercurrent multiplier) and the flow of blood through the vasa recta blood vessels (countercurrent exchanger)• The solute concentration in the loop of Henle ranges from 300 mOsm to 1200 mOsm
  89. 89.  Countercurrent exchange Countercurrent exchange is a common process in the vascular system. Blood flows in opposite directions along juxtaposed decending (arterial) and ascending (venous) vasa recta, and solutes and water are Exchanged between these capillary blood vessels. Countercurrent multiplication Countercurrent multiplication is the process where by a small gradient established at any level of the loop of Henle is increased (maltiplied) into a much larger gradient along the axis of the loop.
  90. 90. Loop of Henle: Countercurrent Multiplication• Vasa Recta prevents loss of medullary osmotic gradient equilibrates with the interstitial fluid • Maintains the osmotic gradient • Delivers blood to the cells in the area• The descending loop: relatively impermeable to solutes, highly permeable to water• The ascending loop: permeable to solutes, impermeable to water• Collecting ducts in the deep medullary regions are permeable to urea
  91. 91. Countercurrent Multiplier and Exchange• Medullary osmotic gradient• H2OECFvasa recta vessels
  92. 92. Formation of Concentrated Urine• ADH (ADH) is the signal to produce concentrated urine it inhibits diuresis• This equalizes the osmolality of the filtrate and the interstitial fluid• In the presence of ADH, 99% of the water in filtrate is reabsorbed
  93. 93. Formation of Dilute Urine• Filtrate is diluted in the ascending loop of Henle if the antidiuretic hormone (ADH) or vasopressin is not secreted• Dilute urine is created by allowing this filtrate to continue into the renal pelvis• Collecting ducts remain impermeable to water; no further water reabsorption occurs• Sodium and selected ions can be removed by active and passive mechanisms• Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
  94. 94. : Mechanism of ADH (Vasopressin) Action: Formation of Water Pores• ADH-dependent water reabsorption is called facultative water reabsorption Figure 20-6: The mechanism of action of vasopressin
  95. 95. Water Balance Reflex:Regulators of Vasopressin Release Figure 20-7: Factors affecting vasopressin release
  96. 96. Regulation of Urine Formation in the Kidney • Way of regulation for urine formation: Filtration, Reabsorption and Secretion • Autoregulation • Solute concentration of tubular fluid Osmotic diuresis -- diabatic、mannitol • Glomerulotubular balance
  97. 97.  Nervous regulation Role of Renal Sympathetic Nerve Reflex of renal sympathetic nerve Reflex of cardiopumonary receptor renorenal reflex Renin-angiotention-aldosterone system
  98. 98. Renin-Angiotension-Aldosterone System
  99. 99. Regulation by ADH• Released by posterior pituitary when osmoreceptors detect an increase in plasma osmolality.• Dehydration or excess salt intake: • Produces sensation of thirst. • Stimulates H20 reabsorption from urine.
  100. 100. The regulation of ADH secretion  Source of ADH Hypothalamus supraoptic and paraventricular nuclei The change of crystal osmotic pressureEffective stimuli The change of effective blood volume
  101. 101. Source of ADH
  102. 102. Effects of ADH on the DCT and Collecting Ducts Figure 26.15a, b
  103. 103. Regulation of ADH release: over hydration
  104. 104. Regulation of release: hypertonicity
  105. 105. Atrial Natriuretic Peptide Activity Increase GFR , reducing water reabsorption Decrease the osmotic gradient of renal medulla and promotes Na+ excretion Acting directly on collecting ducts to inhibit Na+ and water reabsorption, promotes Na+ and water excretion in the urine by the kidney Inhibition renin release and decrease angiotensin II and aldosterone, promotes Na+ excretion
  106. 106.  Endothelin (ET) Constriction blood vessels, decrease GFR Nitic Oxide (NO) Dilation blood vessels, increase GFR Epinephrine (EP), Norepinephrine (NE) promote Na+ and water reabsorption Prostaglandin E2 ,I2 Dilation blood vessels, excretion Na+ and water.
  107. 107. A Summary of Renal Function Figure 26.16a
  108. 108. Renal clearance1. Concept:Renal clearance of any substance is the volume ofplasma that is completely cleaned of the substance bythe kidneys per unit time (min)2. Calculate concentration of it in urine ×urine volume C= concentration of it in plasma
  109. 109. Renal ClearanceRC = UV/P RC = renal clearance rate U = concentration (mg/ml) of the substance in urine V = flow rate of urine formation (ml/min) P = concentration of the same substance in plasma• Renal clearance tests are used to: • Determine the GFR • Detect glomerular damage • Follow the progress of diagnosed renal disease
  110. 110. Theoretical significance of clearance3.1 Measure GFR• A substance---freely filtered, non reabsorbed, non secreted--its renal clearance = GFR• Clearance of inulin or creatinine can be used to estimate GFR
  111. 111. 3.2 Calculate RPF and RBFA substance--freely filtered, non reabsorbed, secretedcompletely from peritubular cells ---a certainconcentration in renal arteries and 0 in venous.Clearance of para-aminohippuric acid (PAH) or diodrastcan be used to calculate RPF.
  112. 112. 3.3 Estimate of tubular handling for a substance If the clearance of substance>125ml/min? ---it must be secreted If it <125ml/min? --- it must be reabsorbed
  113. 113. Physical Characteristics of Urine Color and transparency • Clear, pale to deep yellow (due to urochrome) • Concentrated urine has a deeper yellow color • Drugs, vitamin supplements, and diet can change the color of urine • Cloudy urine may indicate infection of the urinary tract pH • Slightly acidic (pH 6) with a range of 4.5 to 8.0 • Diet can alter pH Specific gravity • Ranges from 1.001 to 1.035 • Is dependent on solute concentration
  114. 114. Chemical Composition of Urine• Urine is 95% water and 5% solutes• Nitrogenous wastes include urea, uric acid, and creatinine• Other normal solutes include: • Sodium, potassium, phosphate, and sulfate ions • Calcium, magnesium, and bicarbonate ions• Abnormally high concentrations of any urinary constituents may indicate pathology
  115. 115. Urine Volume and Micturition1. Urine volume Normal volume : 1.0~2.0L/day Obligatory urine volume ~400ml/day Minimum needed to excrete metabolic wastes of waste products in body. Oliguria--- urine volume < 400ml/day Anuria---urine volume < 100ml/day Accumulation of waste products in body. Polyuria--- urine volume > 2500ml/day long time Abnormal urine volume: Losing water and electrolytes.
  116. 116. MicturitionFunctions of ureters and bladder:Urine flow through ureters to bladder ispropelled by contractions of ureter-wallsmooth muscle.Urine is stored in bladder and intermittentlyejected during urination, or micturition.
  117. 117. Micturition• Micturition is process of emptying the urinary bladder• Two steps are involved:• (1) bladder is filled progressively until its pressure rises• above a threshold level (400~500ml);• (2) a nervous reflex called micturition reflex occurs that empties bladder.
  118. 118. Micturition• Pressure-Volume curve of the bladder has a characteristic shape.• There is a long flat segment as the initial increments of urine enter the bladder and then a sudden sharp rise as the micturition reflex is triggered.
  119. 119. Pressure-volume graph for normal human bladder 1.25 1.00Pressure (kPa) Discomfort Sense of 0.75 1st desire urgency to empty bladder 0.50 0.25 100 200 300 400 Volume (ml)
  120. 120. Micturition (Voiding or Urination)• Bladder can hold 250 - 400ml• Greater volumes stretch bladder walls initiates micturation reflex:• Spinal reflex • Parasympathetic stimulation causes bladder to contract • Internal sphincter opens • External sphincter relaxes due to inhibition
  121. 121. Innervation of bladder
  122. 122. Urination: Micturation reflex Figure 19-18: The micturition reflex
  123. 123. Micturition (Voiding or Urination) Figure 25.20a, b
  124. 124. Review QuestionsExplain concepts1.Glomerular filtration rate2. Effective filtration pressure3. Filtration fraction4.Renal glucose threshold5.Osmotic diuresis6.Renal clearance
  125. 125. Review Questions1. What are the functions of the kidneys?2. Describe autoregulation of renal plasma flow.3. What are three basic processes for urine formation?4. Describe the forces affecting glomerular filtration.5. Describe the factors affecting GFR.6. What is the mechanism of sodium reabsorption in the proximal tubules ?
  126. 126. Review Questions7. What is the mechanism of hydrogen ion secretion and bicarbonate reabsorption?8. What is the mechanism of formation of concentrated and diluted urine?9. After drinking large amount of water, what does the amount of urine change? Why?10. Why a patient with diabetes has glucosuria and polyuria?