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Urine Formation by the Kidneys: I. Glomerular Filtration, Renal Blood Flow and Their Control

Urine Formation by the Kidneys: I. Glomerular Filtration, Renal Blood Flow and Their Control. L1- L2. University of Jordan Faculty of Medicine Department of Physiology and Biochemistry Renal Physiology ( Dental ) spring 2014 Textbook : Textbook of Medical Physiology

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Urine Formation by the Kidneys: I. Glomerular Filtration, Renal Blood Flow and Their Control

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  1. Urine Formation by the Kidneys: I. Glomerular Filtration, Renal Blood Flow and Their Control L1- L2

  2. University of Jordan Faculty of Medicine Department of Physiology and Biochemistry Renal Physiology (Dental) spring 2014 Textbook: Textbook of Medical Physiology By : Arthur C. Guyton and John E. Hall, 12th ed. 2011 ***************************************************************** Lect. No. Topic12th Ed. 1-2 Glomerular Filtration, Renal 303-307 Blood Flow and their Control 310-321 3-5 Tubular Reabsorption and 323-343 Secretion 6-7 Urine concentration and Dilution 345-360 8 Acid-Base Regulation 379-392 9. Micturition 307-310 Faisal I. Mohammed. MD, PhD Email: fmmed@ju.edu.jo Optional Reading: 1. Physiology, by: Robert Berne & Matthew Levy, 6th. ed. 2010 2. Human physiology, by: Lauralee Sherwood, last edition.

  3. Objectives • List the functions of the renal system • Describe the processes of urine formation • Describe glomerular filtration • Explain the control of glomerular filtration • Describe renal blood flow and its control • Explain the glomerulotubular feedback mechanism as a way for control of GFR.

  4. Body fluid regulation.

  5. Summary of Kidney Functions • Excretion of metabolic waste products • urea,creatinine, bilirubin, hydrogen • Excretion of foreign chemicals:drugs, toxins, • pesticides, food additives • Secretion, metabolism, and excretion of hormones • - renal erythropoetic factor • - 1,25 dihydroxycholecalciferol (Vitamin D) • - renin • Regulation of acid-base balance • Gluconeogenesis: glucose synthesis from • amino acids • Control of arterial pressure • Regulation of water & electrolyte excretion

  6. Excretion of Metabolic Waste Products • Urea (from protein metabolism) • Uric acid (from nucleic acid metabolism) • Creatinine (from muscle metabolism) • Bilirubin (from hemoglobin metabolism)

  7. Excretion of Foreign Chemicals • Pesticides • Food additives • Toxins • Drugs

  8. Secretion, Metabolism, and Excretion of Hormones Hormones produced in the kidney • Renal erythropoetic factor • 1,25 dihydroxycholecalciferol (Vitamin D) • Renin Hormones metabolized and excreted by the kidney • Most peptide hormones (e.g. insulin, angiotensin II, etc.)

  9. Regulation of Erythrocyte Production Erythropoetin O2 Delivery Kidney Erythrocyte Production in Bone Marrow

  10. Regulation of Vitamin D Activity • Kidney produces active form of vitamin D • (1,25 dihydroxy vitamin D3 ) • Vitamin D3 is important in calcium and • phosphate metabolism

  11. Regulation of Acid-Base Balance • Excrete acids (kidneys are the only means • of excreting non-volatile acids) • Regulate body fluid buffers • (e.g. Bicarbonate)

  12. Glucose Synthesis Gluconeogenesis: kidneys synthesize glucose from precursors (e.g., amino acids) during prolonged fasting

  13. Regulation of Arterial Pressure • Endocrine Organ • renin-angiotensin system • prostaglandins • kallikrein-kinin system • Control of Extracellular Fluid Volume

  14. Regulation of Water and Electrolyte Balances • Sodium and Water • Potassium • Hydrogen Ions • Calcium, Phosphate, Magnesium

  15. Organs of the urinary system University of Jordan University of Jordan 15

  16. Internal anatomy of the kidneys 16 University of Jordan University of Jordan

  17. Blood supply of the kidneys 17 University of Jordan University of Jordan

  18. Nephron Tubular Segments

  19. Cortical and juxtamedullary nephrons

  20. Basic Mechanisms of Urine Formation

  21. 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 21 21 University of Jordan University of Jordan

  22. Excretion = Filtration - Reabsorption + Secretion Filtration : somewhat variable, not selective (except for proteins), averages 20% of renal plasma flow Reabsorption : highly variable and selective most electrolytes (e.g. Na+, K+, Cl-) and nutritional substances (e.g. glucose) are almost completely reabsorbed; most waste products (e.g. urea) poorly reabsorbed Secretion : highlyvariable; important for rapidly excreting some waste products (e.g. H+), foreign substances (including drugs), and toxins

  23. Renal Handling of Different Substances

  24. Renal Handling of Water and Solutes Filtration Reabsorption Excretion Water 180 179 (liters/day) 1 Sodium 25,560 25,410 (mmol/day) 150 0 Glucose180 180 (gm/day) 0 Creatinine 1.8 1.8 (gm/day)

  25. 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)

  26. Glomerular capillary filtration barrier

  27. Effects of size and electrical charge of dextran on filterability by glomerular capillaries.

  28. Clinical Significance of Proteinuria • Early detection of renal disease in at-risk patients • hypertension: hypertensive renal disease • diabetes: diabetic nephropathy • pregnancy: gestational proteinuric hypertension (pre-eclampsia) • annual “check-up”: renal disease can be silent • Assessment and monitoring of known renal disease

  29. Microalbuminuria • Definition: urine excretion of > 30 but < 150 • mg albumin per day • Causes: early diabetes, hypertension, glomerular hyperfiltration • Prognostic Value: diabetic patients with • microalbuminuria are 10-20 fold more • likely to develop persistent proteinuria

  30. Determinants of GlomerularFiltration Rate

  31. Determinants of Glomerular Filtration Rate Normal Values: GFR = 125 ml/min Net Filt. Press = 10 mmHg Kf = 12.5 ml/min per mmHg, or 4.2 ml/min per mmHg/ 100gm (400 x greater than in many tissues)

  32. Glomerular Capillary Filtration Coefficient (Kf) • Kf = hydraulic conductivity x • surface area • Normally not highly variable • Disease that can reduce Kf and GFR • - chronic hypertension • - obesity / diabetes mellitus • - glomerulonephritis

  33. Glomerular Injury in Chronic Diabetes

  34. Bowman’s Capsule hydrostatic Pressure (PB) • Normally changes as a function of GFR, • not a physiological regulator of GFR • Tubular Obstruction • kidney stones • tubular necrosis • Urinary tract obstruction • Prostate hypertrophy/cancer

  35. Factors Influencing Glomerular Capillary Oncotic Pressure ( G) • Filtration Fraction (FF) • FF G • Arterial Plasma Oncotic Pressure (A) • A G FF = GFR / Renal plasma flow = 125 / 650 ~ 0.2 (or 20%)

  36. Increase in colloid osmotic pressure in plasma flowing through glomerular capillary

  37. Net Filtration Pressure Decreases Along the Glomerulus Because of Increasing Glomerular Colloid Osmotic Pressure Net Filtration Pressure 14 PG = 60 G = 36 PG = 60 G = 28 6 PB = 18

  38. Factors Influencing Glomerular Capillary Oncotic Pressure ( G) • Plasma Protein Concentration • Arterial Plasma Oncotic Pressure (A) • A G • Filtration Fraction (FF) • FF G FF= GFR / Renal plasma flow

  39. Glomerular Hydrostatic Pressure (PG) • Is the determinant of GFR most subject • to physiological control • Factors that influence PG • - arterial pressure (effect is buffered by autoregulation) • - afferent arteriolar resistance • - efferent arteriolar resistance

  40. Kidney disease 150 200 50 100 Autoregulation of Glomerular Hydrostatic Pressure 80 Normal kidney Glomerular Hydrostatic Pressure (mmHg) 60 40 20 0 Arterial Pressure (mmHg)

  41. Autoregulation of renal blood flow and GFR but not urine flow

  42. Effect of afferent and efferent arteriolar constriction on glomerular pressure Ra Re PG PG Blood Flow Blood Flow GFR GFR Ra GFR + Renal Blood Flow Re GFR + Renal Blood Flow

  43. Effect of changes in afferent arteriolaror efferent arteriolar resistance

  44. + PG G determined by : FF = GFR / RPF RBF G _ GFR RE

  45. Summary of Determinants of GFR Kf GFR PB GFR G GFR A G FF G PG GFR RA PG RE PG GFR GFR GFR (as long as RE < 3-4 x normal)

  46. Determinants of Renal Blood Flow (RBF) RBF = P / R P = difference between renal artery pressure and renal vein pressure R = total renal vascular resistance = Ra + Re + Rv = sum of all resistances in kidney vasculature

  47. Renal blood flow • High blood flow (~22 % of cardiac output) • High blood flow needed for high GFR • Oxygen and nutrients delivered to kidneys normally greatly exceeds their metabolic needs • A large fraction of renal oxygen consumption is related to renal tubular sodium reabsorption

  48. Renal oxygen consumption and sodium reabsorption

  49. Control of GFR and renal blood flow • Neurohumoral • Local (Intrinsic)

  50. Control of GFR and renal blood flow 1. Sympathetic Nervous System /catecholamines RA + RE GFR + RBF e.g. severe hemorrhage 2. Angiotensin II RE GFR + RBF (prevents a decrease in GFR) e.g. low sodium diet, volume depletion

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