Renal Structure and Function Sodium Transport UTSouthwestern STARS Program Orson W. Moe, M.D. Department of Internal Medicine Division of Nephrology
organism world Composition Quantity Maintain constancy
Afferent Sensor Physiologic parameter Efferent Effector Disease
Renal Function Good stuff Bad stuff Endocrine hormone Metabolic substrate Excretion Endocrine Metabolism
Gross anatomy
Medulla Outer Outer stripe Inner stripe Inner Medulla (Pyramids) Papilla Capsule Medullary rays Cortex Renal pelvis Ureter Major calyx Column of Bertin Minor calyx
Renal Vasculature Afferent arteriole Arcuate Cortical ascending Renal artery Segmental branches Main branch Interlobar Interlobar Arcuate
Cortical ascending Afferent arteriole Arcuate Efferent arteriole
Renal Circulation Little or no anastomoses Highest blood flow per gram tissue Multiple capillaries in tandem Functional arteriovenous shunts
Renal Circulation Little or no anastomoses Highest flow per gram tissue Multiple capillaries in tandem Functional AV shunts
Renal Circulation Little or no anastomoses Highest flow per gram tissue Multiple capillaries in tandem Functional AV shunts 25-30% Cardiac output <2% Body mass Renal venous po 2 Highest (60-70 mm Hg) Renal A-VO 2 difference Lowest (10-15%)
Glomerular capillary Peritubular capillary Renal Circulation Little or no anastomoses Highest flow per gram tissue Multiple capillaries in tandem Functional AV shunts
Functional AV shunts Renal Circulation Little or no anastomoses Highest flow per gram tissue Multiple capillaries in tandem Functional AV shunts Cortical ascending Afferent arteriole Glomerular capillary Efferent arteriole Peritubular capillary Vasa recta
Excretion Ultrafiltration Secretion Reabsorption
Nephron Secretory Filtration-Reabsorption
Nephron Secretory Dump Filtration-Reabsorption
Nephron Secretory Dump Filtration-Reabsorption
300 marbles Remove 294
300 marbles Remove 294
300 marbles Remove 294 Put 6 back
What does that mean? 5% error 1 L/day 1 L/day 0.95 L/day 0.95 L/day Error = 50 ml 170 L/day 5% error 1 L/day 10 L/day Error = 9L 169 L/day 160 L/day
Filtration-Secretion Fractional excretion Amount excreted Amount filtered Amount filtered Amount excreted > 1 Filtration Amount filtered Amount excreted = 1 Filtration-Reabsorption Amount filtered Amount excreted < 1
Walk the nephron
Overview Distal convoluted tubule Cortical collecting tubule Afferent arteriole Cortical nephron Glomerulus Juxtamedullary nephron Proximal convoluted tubule Efferent arteriole Proximal straight tubule Proximal convoluted tubule Cortex Proximal straight tubule Descending thin limb Thick ascending limb Medullary collecting tubule Outer Medulla Loop of Henle Thin ascending limb Inner Medulla
The Glomerulus Form an ultrafiltrate
Afferent arteriole Parietal epithelium Visceral epithelium Tubule Bowman s space Urinary lumen Efferent arteriole GBM Mesangium
Tubule lumen Visceral epithelial cells (podocytes) Bowman's space Bowman's capsule Parietal epithelial cells Visceral epithelial cell (foot processes) Capillary basement membrane Capillary endothelial cells Nerve fibers Afferent arteriole Juxtaglomerular granular cells Macula densa cells Glomerular capillary lumen Mesangial extracellular matrix Mesangial cells Smooth muscle cells Efferent arteriole Distal end of the thick ascending limb Extraglomerular mesangium
Bowman space Podocyte Capillary
Foot process Podocyte Endothelial cell Mesangial matrix Mesangial cell
Podocyte Foot process Endothelium
Blood cells Large proteins Small proteins Electrolytes Water Basement membrane Endothelium Podocyte foot process
Transition to tubule
Renal Tubules Modify the ultrafiltrate into final urine
Overview Distal convoluted tubule Cortical collecting tubule Afferent arteriole Cortical nephron Glomerulus Juxtamedullary nephron Proximal convoluted tubule Efferent arteriole Proximal straight tubule Proximal convoluted tubule Cortex Proximal straight tubule Descending thin limb Thick ascending limb Medullary collecting tubule Outer Medulla Loop of Henle Thin ascending limb Inner Medulla
Proximal straight tubule Proximal convoluted tubule Distal tubule Intercalated Principal cell cell Cortical collecting tubule Thick ascending limb Inner medullary collecting tubule Descending thin limb Ascending thin limb
Transport Transcellular Paracellular Protrusions Brush border Features of tubular epithelia Tight junctions Intercellular space Infoldings Interdigitation Polarized Apical Basolateral Amplification of surface area Brush border Infolding Interdigitation
Currency for Solute Transport High energy metabolic substrates ATP Electrochemical gradients
Glutamine ATP 3Na + Urine 2K + Low [Na + ] -ve voltage Interstitium/ Plasma
ATPase Na + Cotransporter Countertransporter H + Channel K + ATP Na + Glucose Na + Na + Coupled Transporters H + OH - Paracellular Transport Proteins Ca 2+ Na + Cl -
NaCl
Yanomami Indians Daily ingestion & excretion Yanomani K + 400-500 meq/day Na + <10 meq/day Dallasite 40 meq/day 200 meq/day
NaCl 100% 50-60% 7-10% 2-5% Cortex Medulla 30% 1-2%
Proximal nephron Distal nephron Transcellular pathway Interstitium/Capillary Paracellular pathway Urinary Lumen Low gradient High capacity High gradient Low capacity
Capillary Cl - 3Na + 3Na + 3Na + ~ ~ ~ Cl - 3Na + ~ 2K 2K + 2K ~2K + + + K + Na + Na + X Na + 2Cl - Na + Cl - Na + Proximal X Lumen Distal Low gradient High capacity High gradient Low capacity
Proximal tubule
Thick ascending limb
Distal convoluted tubule
Collecting tubule
Afferent Sensor Physiologic parameter Efferent Effector Disease Ultrafiltrate Urine