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Renal system –L1

Renal system –L1. Faisal I. Mohammed, MD, PhD. University of Jordan. 1. 1. Objectives. List the functions of the renal system Give an anatomical overview of the urinary system Describe the renal system functional unit –Nephron- and its types

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Renal system –L1

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  1. Renal system –L1 Faisal I. Mohammed, MD, PhD University of Jordan University of Jordan 1 1

  2. Objectives • List the functions of the renal system • Give an anatomical overview of the urinary system • Describe the renal system functional unit –Nephron- and its types • Outline the process of urine formation and define GFR • Introduce the principle of clearance • Describe GFR regulation 2 University of Jordan University of Jordan

  3. Overview of kidney functions • Regulation of blood ionic composition • Regulation of blood pH • Regulation of blood volume • Regulation of blood pressure • Maintenance of blood osmolarity • Production of hormones (calcitrol and erythropoitin) • Regulation of blood glucose level • Excretion of wastes from metabolic reactions and foreign substances (drugs or toxins) 3 3 University of Jordan University of Jordan

  4. Organs of the urinary system University of Jordan University of Jordan 4

  5. Internal anatomy of the kidneys 5 University of Jordan University of Jordan

  6. Blood and nerve supply of the kidneys • Blood supply • Although kidneys constitute less than 0.5% of total body mass, they receive 20-25% of resting cardiac output • Left and right renal artery enters kidney • Branches into segmental, interlobar, arcuate, interlobular arteries • Each nephron receives one afferent arteriole • Divides into glomerulus – capillary ball • Reunite to form efferent arteriole (unique) • Divide to form peritubular capillaries or some have vasa recta • Peritubular venule, interlobar vein and renal vein exits kidney • Renal nerves are part of the sympathetic autonomic nervous system • Most are vasomotor nerves regulating blood flow 6 6 University of Jordan University of Jordan

  7. Blood supply of the kidneys 7 University of Jordan University of Jordan

  8. The nephron – functional units of kidney 2 parts • Renal corpuscle – filters blood plasma • Glomerulus – capillary network • Glomerular (Bowman’s) capsule – double-walled cup surrounding glomerulus • Renal tubule – filtered fluid passes into • Proximal convoluted tubule • Descending and ascending loop of Henle (nephron loop) • Distal convoluted tubule 8 8 University of Jordan University of Jordan

  9. Nephrons • Renal corpuscle and both convoluted tubules in cortex, loop of Henle extend into medulla • Distal convoluted tubule of several nephrons empty into single collecting duct • Cortical nephrons – 80-85% of nephrons • Renal corpuscle in outer portion of cortex and short loops of Henle extend only into outer region of medulla • Juxtamedullary nephrons – other 25-20% • Renal corpuscle deep in cortex and long loops of Henle extend deep into medulla • Receive blood from peritubular capillaries and vasa recta • Ascending limb has thick and thin regions • Enable kidney to secrete very dilute or very concentrated urine 9 9 University of Jordan University of Jordan

  10. Cortical Nephron 10 University of Jordan University of Jordan

  11. Juxtamedullary Nephron 11 University of Jordan University of Jordan

  12. Histology of nephron and collecting duct • Glomerular capsule • Visceral layer has podocytes that wrap projections around single layer of endothelial cells of glomerular capillaries and form inner wall of capsule • Parietal layer forms outer wall of capsule • Fluid filtered from glomerular capillaries enters capsular (Bowman’s) space 12 12 University of Jordan University of Jordan

  13. Renal corpuscle 13 University of Jordan University of Jordan

  14. Renal tubule and collecting duct • Proximal convoluted tubule cells have microvilli with brush border – increases surface area • Juxtaglomerular appraratus helps regulate blood pressure in kidney • Macula densa – cells in final part of ascending loop of Henle • Juxtaglomerular cells – cells of afferent and efferent arterioles contain modified smooth muscle fibers • Last part of distal convoluted tubule and collecting duct • Principal cells – receptors for antidiuretic hormone (ADH) and aldosterone • Intercalated cells – role in blood pH homeostasis 14 14 University of Jordan University of Jordan

  15. Overview of renal physiology • Glomerular filtration • Water and most solutes in blood plasma move across the wall of the glomerular capillaries into glomerular capsule and then renal tubule • Tubular reabsorption • As filtered fluid moves along tubule and through collecting duct, about 99% of water and many useful solutes reabsorbed – returned to blood • Tubular secretion • As filtered fluid moves along tubule and through collecting duct, other material secreted into fluid such as wastes, drugs, and excess ions – removes substances from blood • Solutes in the fluid that drains into the renal pelvis remain in the fluid and are excreted • Excretion of any solute = glomerular filtration + secretion - reabsorption 15 15 University of Jordan University of Jordan

  16. Renal tubule and collecting duct Renal tubule and collecting duct Renal tubule and collecting duct Renal corpuscle Renal corpuscle Renal corpuscle Afferent arteriole Afferent arteriole Afferent arteriole Glomerular capsule Glomerular capsule Glomerular capsule Urine (contains excreted substances) Urine (contains excreted substances) Urine (contains excreted substances) Fluid in renal tubule Fluid in renal tubule Fluid in renal tubule 1 1 1 Filtration from blood plasma into nephron Filtration from blood plasma into nephron Filtration from blood plasma into nephron 2 2 3 Tubular reabsorption from fluid into blood Tubular reabsorption from fluid into blood Tubular secretion from blood into fluid Efferent arteriole Efferent arteriole Efferent arteriole Blood (contains reabsorbed substances) Blood (contains reabsorbed substances) Blood (contains reabsorbed substances) Peritubular capillaries Peritubular capillaries Peritubular capillaries Structures and functions of a nephron 16 16 University of Jordan University of Jordan

  17. Glomerular Filtration GFR = 125 ml/min = 180 liters/day • Plasma volume is filtered 60 times per day • Glomerular filtrate composition is about the • same as plasma, except for large proteins • Filtration fraction (GFR / Renal Plasma Flow) • = 0.2 (i.e. 20% of plasma is filtered) University of Jordan

  18. Glomerular filtration • Glomerular filtrate – fluid that enters capsular space • Daily volume 150-180 liters – more than 99% returned to blood plasma via tubular reabsorption • Filtration membrane – endothelial cells of glomerular capillaries and podocytes encircling capillaries • Permits filtration of water and small solutes • Prevents filtration of most plasma proteins, blood cells and platelets • 3 barriers to cross – glomerular endothelial cells fenestrations, basal lamina between endothelium and podocytes and pedicels of podocytes create filtration slits • Volume of fluid filtered is large because of large surface area, thin and porous membrane, and high glomerular capillary blood pressure 18 18 University of Jordan University of Jordan

  19. Podocyte of visceral layer of glomerular (Bowman’s) capsule Podocyte of visceral layer of glomerular (Bowman’s) capsule Podocyte of visceral layer of glomerular (Bowman’s) capsule Filtration slit Filtration slit Filtration slit Pedicel Pedicel Pedicel 1 1 1 Fenestration (pore) of glomerular endothelial cell: prevents filtration of blood cells but allows all components of blood plasma to pass through Fenestration (pore) of glomerular endothelial cell: prevents filtration of blood cells but allows all components of blood plasma to pass through Fenestration (pore) of glomerular endothelial cell: prevents filtration of blood cells but allows all components of blood plasma to pass through 2 2 Basal lamina of glomerulus: prevents filtration of larger proteins Basal lamina of glomerulus: prevents filtration of larger proteins 3 Slit membrane between pedicels: prevents filtration of medium-sized proteins (a) Details of filtration membrane (a) Details of filtration membrane (a) Details of filtration membrane Pedicel of podocyte Pedicel of podocyte Pedicel of podocyte Filtration slit Filtration slit Filtration slit Basal lamina Basal lamina Basal lamina Lumen of glomerulus Lumen of glomerulus Lumen of glomerulus 78,000x 78,000x 78,000x TEM TEM TEM Fenestration (pore) of glomerular endothelial cell Fenestration (pore) of glomerular endothelial cell Fenestration (pore) of glomerular endothelial cell (b) Filtration membrane (b) Filtration membrane (b) Filtration membrane The filtration membrane 19 19 University of Jordan University of Jordan

  20. Glomerular Filtration University of Jordan

  21. Net filtration pressure • Net filtration pressure (NFP) is the total pressure that promotes filtration • NFP = GBHP – CHP – BCOP • Glomerular blood hydrostatic pressure is the blood pressure of the glomerular capillaries forcing water and solutes through filtration slits • Capsular hydrostatic pressure is the hydrostatic pressure exerted against the filtration membrane by fluid already in the capsular space and represents “back pressure” • Blood colloid osmotic pressure due to presence of proteins in blood plasma and also opposes filtration 21 21 University of Jordan University of Jordan

  22. 1 1 1 GLOMERULAR BLOOD HYDROSTATIC PRESSURE (GBHP) = 55 mmHg GLOMERULAR BLOOD HYDROSTATIC PRESSURE (GBHP) = 55 mmHg GLOMERULAR BLOOD HYDROSTATIC PRESSURE (GBHP) = 55 mmHg 2 2 CAPSULAR HYDROSTATIC PRESSURE (CHP) = 15 mmHg CAPSULAR HYDROSTATIC PRESSURE (CHP) = 15 mmHg 3 BLOOD COLLOID OSMOTIC PRESSURE (BCOP) = 30 mmHg Afferent arteriole Afferent arteriole Afferent arteriole Proximal convoluted tubule Proximal convoluted tubule Proximal convoluted tubule Efferent arteriole Efferent arteriole Efferent arteriole NET FILTRATION PRESSURE (NFP) =GBHP – CHP – BCOP = 55 mmHg 15 mmHg 30 mmHg = 10 mmHg NET FILTRATION PRESSURE (NFP) =GBHP – CHP – BCOP = 55 mmHg 15 mmHg 30 mmHg = 10 mmHg NET FILTRATION PRESSURE (NFP) =GBHP – CHP – BCOP = 55 mmHg 15 mmHg 30 mmHg = 10 mmHg Glomerular (Bowman's) capsule Glomerular (Bowman's) capsule Glomerular (Bowman's) capsule Capsular space Capsular space Capsular space The pressures that drive glomerular filtration 22 22 University of Jordan University of Jordan

  23. Glomerular filtration • Glomerular filtration rate – amount of filtrate formed in all the renal corpuscles of both kidneys each minute • Homeostasis requires kidneys maintain a relatively constant GFR • Too high – substances pass too quickly and are not reabsorbed • Too low – nearly all reabsorbed and some waste products not adequately excreted • GFR directly related to pressures that determine net filtration pressure 23 23 University of Jordan University of Jordan

  24. Clearance • “Clearance” describes the rate at which substances • are removed (cleared) from the plasma. • Renal clearance of a substance is the volume of • plasma completely cleared of a substance • per min by the kidneys. University of Jordan

  25. Cs = Us x V = urine excretion rate s Ps Plasma conc. s Clearance Technique Renal clearance (Cs) of a substance is the volume of plasma completely cleared of a substance per min. Cs x Ps = Us x V Where : Cs = clearance of substance S Ps = plasma conc. of substance S Us = urine conc. of substance S V = urine flow rate University of Jordan

  26. GFR x Pin = Uin x V Uin x V GFR = Pin Use of Clearance to Measure GFR For a substance that is freely filtered, but not reabsorbed or secreted (inulin, 125 I-iothalamate, creatinine), renal clearance is equal to GFR amount filtered = amount excreted University of Jordan

  27. Uin x V GFR = Cinulin = Pin 125 x 1.0 = 125 ml/min GFR = 1.0 Calculate the GFR from the following data: Pinulin = 1.0 mg / 100ml Uinulin = 125 mg/100 ml Urine flow rate = 1.0 ml/min University of Jordan

  28. Use of Clearance to Estimate Renal Plasma Flow Theoretically, if a substance is completely cleared from the plasma, its clearance rate would equal renal plasma flow Cx = renal plasma flow University of Jordan

  29. ~ 2. amount entered = amount excreted UPAH x V ERPF = PPAH Use of PAH Clearance to Estimate Renal Plasma Flow Paraminohippuric acid (PAH) is freely filtered and secreted and is almost completely cleared from the renal plasma 1. amount enter kidney = RPF x PPAH 3. ERPF x Ppah = UPAH x V ~ 10 % PAH remains ERPF = Clearance PAH University of Jordan

  30. Calculation of Tubular Reabsorption Reabsorption = Filtration -Excretion Filt s = GFR x Ps Excrets= Us x V University of Jordan

  31. Calculation of Tubular Secretion Secretion = Excretion - Filtration Filt s = GFR x Ps VPAH = 0.1 Excret s = Us x V University of Jordan

  32. Use of Clearance to Estimate Renal Plasma Flow Theoretically, if a substance is completely cleared from the plasma, its clearance rate would equal renal plasma flow Cx = renal plasma flow University of Jordan

  33. Clearances of Different Substances Substance Clearance (ml/min inulin 125 PAH 600 glucose 0 sodium 0.9 urea 70 Clearance of inulin (Cin) = GFR if Cx < Cin : indicates reabsorption of x if Cx > Cin : indicates secretion of x Clearance creatinine (Ccreat) ~ 140 (used to estimate GFR) Clearance of PAH (Cpah) ~ effective renal plasma flow University of Jordan

  34. GFR regulation : Adjusting blood flow • GFR is regulated using three mechanisms • 1. Renal Autoregulation • 2. Neural regulation • 3. Hormonal regulation • All three mechanism adjust renal blood pressure and resulting blood flow University of Jordan

  35. Local Control of GFR and renal blood flow • 1. Autoregulation of GFR and Renal Blood Flow • Myogenic Mechanism • Macula Densa Feedback • (tubuloglomerular feedback) • Angiotensin II ( contributes to GFR but • not RBF autoregulation) University of Jordan

  36. 120 80 Renal Autoregulation 100 Renal Artery Pressure (mmHg) Glomerular Filtration Rate Renal Blood Flow 0 1 2 3 4 5 University of Jordan Time (min)

  37. 3 Mechanisms regulating GFR • Renal autoregulation • Kidneys themselves maintain constant renal blood flow and GFR using • Myogenic mechanism – occurs when stretching triggers contraction of smooth muscle cells in afferent arterioles – reduces GFR • Tubuloglomerular mechanism – macula densa provides feedback to glomerulus, inhibits release of NO causing afferent arterioles to constrict and decreasing GFR 37 37 University of Jordan University of Jordan

  38. Myogenic Mechanism Stretch of Blood Vessel Cell Ca++ Entry Vascular Resistance Intracell. Ca++ Arterial Pressure Blood Flow and GFR University of Jordan

  39. Structure of the juxtaglomerular apparatus:macula densa University of Jordan

  40. Macula Densa Feedback GFR Distal NaCl Delivery Macula Densa NaCl Reabsorption (macula densa feedback) Afferent Arteriolar Resistance University of Jordan

  41. Macula Densa Feedback Proximal NaCl Reabsorption Distal NaCl Delivery Macula Densa NaCl Reabsorption (macula densa feedback) Afferent Arteriolar Resistance GFR University of Jordan

  42. Renin Blood AngII Pressure Efferent Arteriolar Resistance Regulation of GFR by Ang II Macula GFR Densa NaCl University of Jordan

  43. . 150 200 50 100 Ang II Blockade Impairs GFR Autoregulation 1600 1200 Renal Blood Flow ( ml/min) 800 Normal Ang II Blockade 400 0 120 Glomerular Filtration Rate (ml/min) 80 40 0 0 Arterial Pressure (mmHg) University of Jordan

  44. Macula densa feedback mechanism for regulating GFR University of Jordan

  45. Tuboglomerular feedback 45 University of Jordan University of Jordan

  46. Mechanisms regulating GFR • Neural regulation • Kidney blood vessels supplied by sympathetic ANS fibers that release norepinephrine causing vasoconstriction • Moderate stimulation – both afferent and efferent arterioles constrict to same degree and GFR decreases • Greater stimulation constricts afferent arterioles more and GFR drops • Hormonal regulation • Angiotensin II reduces GFR – potent vasoconstrictor of both afferent and efferent arterioles • Atrial natriuretic peptide increases GFR – stretching of atria causes release, increases capillary surface area for filtration 46 46 University of Jordan University of Jordan

  47. Summary of neurohumoral control of GFR and renal blood flow Effect on GFR Effect on RBF Sympathetic activity Catecholamines Angiotensin II EDRF (NO) Endothelin Prostaglandins no change decrease increase University of Jordan

  48. Thank You University of Jordan

  49. Renal system –L3 Faisal I. Mohammed, MD, PhD University of Jordan University of Jordan 49 49

  50. Tubular reabsorption and tubular secretion • Reabsorption – return of most of the filtered water and many solutes to the bloodstream • About 99% of filtered water reabsorbed • Proximal convoluted tubule cells make largest contribution around 67% • Both active and passive processes • Secretion – transfer of material from blood into tubular fluid • Helps control blood pH • Helps eliminate substances from the body 50 50 University of Jordan University of Jordan

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