Renal Physiology (II) - Glomerular Structure & Filtration

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by dr Mohammed Abel Gawad (drgawad@gmail.com): Nephrology Specialist at Kidney & Urology Center - Alexandria - Egypt. website: www.nephrotube.blogspot.com

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Renal Physiology (II) - Glomerular Structure & Filtration

  1. 1. 1 RENAL PHYSIOLOGY (II) m GLOMERULARSTRUCTURE & FILTRATION Mohammed Abdel Gawad
  2. 2. OBJECTIVES2  Be sure that you know what is NEPHRON  Be sure that you know RENAL CIRCULATION  Formation of URINE Steps (General Aspect)  Glomerular Filtration Barrier  Glomerular Filtrate & GFR (definitions)  Starling’s Forces & Membrane Permeability  Dynamics of Glomerular Filtration  Glomerular Filtrate & Kf (definitions)  Autoregulation of GFR  Factors affecting GFR
  3. 3. OBJECTIVES3  Be sure that you know what is NEPHRON  Be sure that you know RENAL CIRCULATION  Formation of URINE Steps (General Aspect)  Glomerular Filtration Barrier  Glomerular Filtrate & GFR (definitions)  Starling’s Forces & Membrane Permeability  Dynamics of Glomerular Filtration  Glomerular Filtrate & Kf (definitions)  Autoregulation of GFR  Factors affecting GFR
  4. 4. NEPHRON (Renal malpighian corpuscle & Renal tubules)4
  5. 5. RENAL CIRCULATION5
  6. 6. OBJECTIVES6  Be sure that you know what is NEPHRON  Be sure that you know RENAL CIRCULATION  Formation of URINE Steps (General Aspect)  Glomerular Filtration Barrier  Glomerular Filtrate & GFR (definitions)  Starling’s Forces & Membrane Permeability  Dynamics of Glomerular Filtration  Glomerular Filtrate & Kf (definitions)  Autoregulation of GFR  Factors affecting GFR
  7. 7. Formation of URINE in 3 steps7 Tubular Tubular Reabsorption SecretionGlomerular Excretion Filtration
  8. 8. Formation of URINE in 3 steps8
  9. 9. Formation of URINE in 3 steps9
  10. 10. OBJECTIVES10  Be sure that you know what is NEPHRON  Be sure that you know RENAL CIRCULATION  Formation of URINE Steps (General Aspect)  Glomerular Filtration Barrier  Glomerular Filtrate & GFR (definitions)  Starling’s Forces & Membrane Permeability  Dynamics of Glomerular Filtration  Glomerular Filtrate & Kf (definitions)  Autoregulation of GFR  Factors affecting GFR
  11. 11. Glomerular Filtration Barrier11
  12. 12. Glomerular Filtration Barrier12 A. The endothelial cells of the glomerulus;  1. pore (fenestra) (70-100 nm) B. Glomerular basement membrane:  1. lamina rara interna  2. lamina densa  3. lamina rara externa C. Podocytes:  1. enzymatic and structural protein  2. filtration slit (20-30 nm)  3. filtration diaphragm (nephrin)
  13. 13. Glomerular Filtration Barrier13
  14. 14. GLOMERULAR BASEMENT MEMBRANESTRUCTURE14 Formed of:  Collagen type IV  Triple helix: 3 α-peptide chains with globular non collagenous domain (NC1) Abnormalities:  Mutation in α-peptide chains → no proper helix → hereditary nephritis  Antibodies against NC1 in kidney → anti GBM disease  Antibodies against NC1 in kidney & lung → Goodpastuer Syndrome
  15. 15. OBJECTIVES15  Be sure that you know what is NEPHRON  Be sure that you know RENAL CIRCULATION  Formation of URINE Steps (General Aspect)  Glomerular Filtration Barrier  Glomerular Filtrate & GFR (definitions)  Starling’s Forces & Membrane Permeability  Dynamics of Glomerular Filtration  Glomerular Filtrate & Kf (definitions)  Autoregulation of GFR  Factors affecting GFR
  16. 16. 16 Glomerular Filtrate & GFR Glomerular filtrate:  fluid that filters through the glomeruli into Bowmans capsule = plasma – (plasma proteins, plasma proteins binbed substances & substances with a MW > 70.000). Glomerular Filtration Rate (GFR):  - definition: The quantity of glomerular filtrate formed in all nephrons of both kidneys / min.  - normal value: 125ml/min. 180 Liters/day.
  17. 17. 17 Glomerular Filtrate & GFR
  18. 18. OBJECTIVES18  Be sure that you know what is NEPHRON  Be sure that you know RENAL CIRCULATION  Formation of URINE Steps (General Aspect)  Glomerular Filtration Barrier  Glomerular Filtrate & GFR (definitions)  Starling’s Forces & Membrane Permeability  Dynamics of Glomerular Filtration  Glomerular Filtrate & Kf (definitions)  Autoregulation of GFR  Factors affecting GFR
  19. 19. Movement of water: Starling’s Forces & Membrane Permeability19 The amount of water in each body compartment is dependent on:  1- osmotic pressure  2- hydrostatic pressure  + Membrane characteristics
  20. 20. Total body water Compartments
  21. 21. Osmolality is the number of particles (mmol) contained in one liter of water, so measured in mmol/L. i.e. it is the concentration by number
  22. 22. Starling’s Forces – Osmotic pressure22
  23. 23. Starling’s Forces – Osmotic pressure23
  24. 24. Starling’s Forces – Hydrostatic pressure24
  25. 25. Starling’s Forces
  26. 26. Membrane Factors Membrane permeability (s) is clinically relevant in disorders which disrupt membrane integrity (e.g., sepsis). Permeability of a membrane ranges from zero, completely permeable, to one, completely impermeable.
  27. 27. Starling’s Forces – Net Filtration Pressure27
  28. 28. Starling’s Forces – Net Filtration Pressure28
  29. 29. Hydrostatic Pressure in Renal Circulation29
  30. 30. DYNAMICS OF GLOMERULAR FILTRATION(STARLING FORCES)(NET FILTRATION PRESSURE)30
  31. 31. DYNAMICS OF GLOMERULAR FILTRATION(STARLING FORCES)(NET FILTRATION PRESSURE)31
  32. 32. GFR & Filtration Coefficient (Kf)32 Glomerular Filtration Rate:  - definition: The quantity of glomerular filtrate formed in all nephrons of both kidneys / min. For the 10 mmHg  - normal value: 125ml/min. 180 Liters/day. Filtration coefficient (Kf):  It is the GFR for both kidneys per mmHg of filtration pressure.  Normally = 12.5 For 1 mmHg  GFR = 12.5 X 10 = 125 ml/min
  33. 33. OBJECTIVES33  Be sure that you know what is NEPHRON  Be sure that you know RENAL CIRCULATION  Formation of URINE Steps (General Aspect)  Glomerular Filtration Barrier  Glomerular Filtrate & GFR (definitions)  Starling’s Forces & Membrane Permeability  Dynamics of Glomerular Filtration  Glomerular Filtrate & Kf (definitions)  Autoregulation of GFR  Factors affecting GFR
  34. 34. Autoregulation of GFR34 Under normal conditions (MAP= 80- 180mmHg) renal autoregulation maintains a nearly constant glomerular filtration rate A- Myogenic mechanism:  Laplace law:  Vessel wall tension α Distending pressure X radius of the vessel.  When arterial pressure rises → afferent arteriole stretches → vascular smooth muscles contract → arteriole resistance offsets pressure increase → RBF (& hence GFR) remain constant & vise versa
  35. 35. Autoregulation of GFR35 B- Tubuloglomerular feed back mechanism
  36. 36. Autoregulation of GFR36 B- Tubuloglomerular feed back mechanism
  37. 37. Autoregulation of GFR37 B- Tubuloglomerular feed back mechanism Juxtaglomerular Apparatus or Complex: is a specialized region of a nephron where the afferent arteriole and Distal Convoluted Tubule (DCT) come in direct contact with each other. Juxtaglomeruar Apparatus (JGA) consists of: 1) Juxtaglomerular cells (modified smooth muscle cells) of afferent arteriole including renin containing (synthesizes and stores renin) and sympathetically innervated granulated cells which function as mechanoreceptors to sense blood pressure. 2) Macula densa cells (Na+ sensors) of Distal Convoluted Tubule (DCT) which function as chemoreceptors to sense changes in the solute concentration and flow rate of filtrate.
  38. 38. Autoregulation of GFR38 B- Tubuloglomerular feed back mechanism
  39. 39. Autoregulation of GFR39 B- Tubuloglomerular feed back mechanism
  40. 40. Autoregulation of GFR40 B- Tubuloglomerular feed back mechanism  See the video on our facebook group NephroTube
  41. 41. OBJECTIVES41  Be sure that you know what is NEPHRON  Be sure that you know RENAL CIRCULATION  Formation of URINE Steps (General Aspect)  Glomerular Filtration Barrier  Glomerular Filtrate & GFR (definitions)  Starling’s Forces & Membrane Permeability  Dynamics of Glomerular Filtration  Glomerular Filtrate & Kf (definitions)  Autoregulation of GFR  Factors affecting GFR
  42. 42. Factors Affecting GFR1. Renal Blood Flow :42 - increase blood flow through the nephrons → elevates the glomerular pressure → increases the glomerular filtration rate.
  43. 43. Factors Affecting GFR2. Diameter of glomerular blood vessels:43 Glomerulus Afferent arteriole Efferent arteriole GFR GFR Glomerular filtrate Eff. Art. Aff. Art. Eff. Art. dilatationAff. Art. dilatation constriction constriction ? Prostaglandins Angiotensin II Adrenaline & Angiotensin II E2 & Noradrenaline (Symp blockadeI2, Kinins, Dopa nerves), Endothelin, mine (low
  44. 44. Factors Affecting GFR2. Diameter of glomerular blood vessels:44 i- mild constriction → increases the glomerular pressure → increases the Eff. Art. filtration rate. constriction ii- severe or moderate constriction → decreases the glomerular flow rate → decreases the filtration rate, because the plasma will remain for a longer period of time in the glomerulus → extra large amounts of plasma will filter out → increases the plasma colloid osmotic pressure → paradoxical decrease in GFR occurs despite the increase in glomeular pressure.
  45. 45. Factors Affecting GFR3. Factors affecting Net Filtration Pressure:45 I. Arterial blood pressure: -a rise in the systemic blood pressure → an auto-regulatory mechanism (automatic afferent arteriolar constriction) → prevents the rise in the glomerular pressure II. Colloid osmotic pressure: -Hypoproteinaemia will increase the filtration rate. III. Post renal obstruction makes back pressure and increases the Bowman’s capsule hydrostatic pressure which leads to decreasing GFR.
  46. 46. Factors Affecting GFR4. Factors affecting filtration coefficient (Kf):46 I. Permeability of Glomerular capillaries (hydrolic conductivity):  - Increase permeability of glomerular capillaries → increases the GFR.  - Normally the permeability of the glomerular capillaries and Bowmans capsule is absent for substances of molecular weight higher than 70,000.  - MW:  Albumin: 70,000  Globulin: 165,000  Fibrinogen: 200,000  Hb:68,000 II- Surface area of the membrane:  if decrease, it will decrease GFR  e.g.  Chronic pyelonephritis  Chronic GN
  47. 47. The Concept Of Plasma47 Clearance  Inulin clearance  Creatinine clearance  PAH clearance
  48. 48. 48 Follow On www.nephrotube.blogspot.com & Facebook Group NephroTube
  49. 49. 49 Gawad

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