Functional morphology of kidneys Clearance Assoc. Prof. MUDr. Markéta Bébarová, Ph.D. Department of Physiology Faculty of Medicine, Masaryk University This presentation includes only the most important terms and facts. Its content by itself is not a sufficient T source of information required to 1 pass the Physiology exam. Renal Functions > Excretion of Waste Products and Toxins > Control of Volume and Composition of Body Fluids, Osmolality > Regulation of Acid-Base Balance > Regulation of Blood Pressure >Secretion, Metabolism and Excretion of Hormones >Glukoneogenesis Structure of Kidney Cortical radiate vein Cortical radiate artery Arcuate vein Arcuate artery Interlobar vein Interlobar artery Segmental arteries Renal vein Renal artery Renal pelvis Ureter Renal medulla Renal cortex (a) Frontal section illustrating major blood vessels 01013 Petfjon Eduutcn ine Aorta Renal artery Segmental artery Interlobar artery Arcuate artery Cortical radiate artery •I" Afferent arteriole L Inferior vena cava í Renal vein í Interlobar vein í Arcuate vein í Cortical radiate vein 4- Peritubular capillaries -or vasa recta í Efferent arteriole Glomerulus (capillaries) J ries)-1 Nephron-associated blood vessels (see Figure 25.7) (b) Path of blood flow through renal blood vessels http://classes.midlandstech.edu/carterp/Courses/bio211/chap25/chap25.htm Structure of Kidney Cortical nephron Juxtamedtillary nephron - Short nephron loop • Long nephron loop • Glomerulus lurtfrer Irom the cortex-medulla junction • Glomerul js closer to the cortex-medulla junction - Efferent arteriole supplies peritubular capillaries ■ Efferent arteriole supplies vasa recta http://classes.mid la ndstech.edu/carter p/Courses/bio211/c hap25/chap25.htm Structure of Nephron thin descending limb Ganong's Review of Medical Physiology, 23rd edition Structure of Nephron - Glomerulus Proximal tubule Podocytes Capillary loops Bowman's space Bowman's capsule B Basal lamina Endothelium Afferent arteriole Efferent arteriole Epithelium Basement membrane Endothelium Basal lamina Endothelium Podocyte mesangial cells Fenestrations Guyton & Hall. Textbook of Medical Physiology Structure of Nephron - Glomerulus Guyton & Hall. Textbook of Medical Physiology C Basal lamina Endothelium " IAS W ' Structure of Nephron - Glomerulus > High filtration rate in glomeruli provided by high permeability of glomerular membrane > Protein passage barrier negative charge of all layers of glomerular membrane 1.0 0 4.0 6.0 8.0 Effective molecular diameter (nm) Ganong's Review of Medical Physiology Structure of Nephron - Tubulus Distal convoluted tubule Proximal convoluted tubule Loop of Henle, thick ascending ** limb I---' Collecting duct Outer medulla Inner medulla > glomerulus > proximal convoluted tubule Loop of Henle, thin descending limb Ganong's Review of Medical Physiology, 23rd edition Proximal convoluted tubule Structure of Nephron - Tubulus Inner medulla Loop of Henle, thin descending limb > glomerulus > proximal convoluted tubule > loop of Henle Loop of Henle, thin descending limb Loop of Henle, thick ascending Ganong's Review of Medical Physiology, 23rd edition limb Structure of Nephron - Tubulus Distal convoluted tubule Proximal convoluted tubule Lo thin ú Collecting duct Renal nerves Efferent arteriole Juxtaglomerular cells merular \ \ v lis * \ Afferent arteriole > glomerulus > proximal convoluted tubule > loop of Henle Loop of Henle, thin descending limb Loop of Henle, thick ascending Ganong's Review of Medical Physiology, 23rd edition limb Structure of Nephron - Tubulus Cortical nephron Juxtamedullary nephron * Short nephron loop * Long nephron loop • Glomerulus further from the cortex-medulla junction " Glomerulus closer to the cortex-medulla |unction ■ Efferent arteriole supplies peritubular capillaries * Efferent arteriole supplies vasa recta Cortical radiate vein Cortical radiate artery Afferent arteriole Collecting duct Efferent arteriole http://classes.midla ndstech.edu/carter p/Courses/bio211/c hap25/chap25.htm - Structure of Nephron - Tubulus Inner medulla > glomerulus > proximal convoluted tubule > loop of Henle > distal convoluted tubule Loop of Henle, thin descending limb Ganong's Review of Medical Physiology, 23rd edition Distal convoluted tubule Structure of Nephron - Tubulus Distal convoluted tubule Proximal convoluted tubule Loop of Henle, thick ascending ** limb I---1 Collecting duct Outer medulla Inner medulla > glomerulus > proximal convoluted tubule > loop of Henle > distal convoluted tubule > collecting duct Loop of Henle, thin descending limb Ganong's Review of Medical Physiology, 23rd edition Collecting duct Urine Formation Afferent arteriole 4 Efferent arteriole Glomerular capillaries Bowman's capsule 1. Filtration 2. Reabsorption 3. Secretion 4. Excretion Peritubular capillaries Renal vein v Urinary excretion Excretion = Filtration - Reabsorption + Secretion Guyton & Hall. Textbook of Medical Physiology 1) Glomerular filtration 2) Tubular reabsorption 3) Tubular secretion 4) Urine excretion A Urine Formation Guyton & Hall. Textbook of Medical Physiology ■ creatinine ■ electrolytes other waste HDroducts C. Filtration, complete D. Filtration, secretion reabsorption t Urine Urine ■ amino acids ■ PAH ■ glucose ■ toxins ■ organic base and acids Urine Formation A. Filtration only Substance A B. Filtration, partial reabsorption C. Filtration, complete reabsorption D. Filtration, secretion Substance Substance C Substance D Urine Urine Guyton & Hall. Textbook of Medical Physiology Urine creatinine other waste products Substance Concentration in Urine (U) Plasma (P) -U/P Ratio Glucose (mg/dL) 0 100 0 Na+ (mEq/L) 90 140 0.6 Urea (mg/dL) 900 15 60 Creatinine (mg/dL) 150 1 150 Urine PAH toxins A organic base and acids Urine Formation - Glomerular Filtration Proximal tubule Podocytes Capillary loops Bowman's space Bowman's capsule B GFR = 125 ml/min = 180 FF = 0.2 20% of plasma filtered! I/day Afferent arteriole Efferent arteriole Epithelium Basement membrane Endothelium Fenestrations 800 r 600 - j 400 200 Renal blood flow Glomerular filtration Guyton & Hall. Textbook of Medical Physiology 70 140 210 Arterial pressure (mm Hg) Ganong's Review of Medical Physiology, 23rd edition Urine Formation - Glomerular Filtration Glomerular filtration rate (GFR) depends on: 1) Capillary filtration coefficient Kf (permeability and area of glomerular membrane; mesangial cells) 2) Balance of hydrostatic and coloid osmotic forces ^ GFR= Kf - net filtration pressure Urine Formation - Glomerular Filtration Glomerular filtration rate (GFR) depends on: 1) Capillary filtration coefficient Kf (permeability and area of glomerular membrane; mesangial cells) 2) Balance of hydrostatic and coloid osmotic forces ^ GFR= Kf - net filtration pressure Urine Formation - Glomerular Filtration GFR = Kr net filtration pressure 800 600 % 400 E 200 Renal blood flow ^/ Afferent arteriole Glomerular filtration 70 140 210 Arterial pressure (mm Hg) Glomerular Glomerular hydrostatic colloid osmotic pressure pressure Hg) (32 mm Hg) Efferent arteriole ~\ (60 mm i Ganong's Review of Medical Physiology, 23rd edition ° Bowman's capsule pressure (18 mm Hg) nB = 0 Guyton & Hall. Textbook of Medical Physiology Under physiological conditions: net filtration pressure = PG + ttb - PB - ttg = 60 + 0 - 18 - 32 = 10 mmHg Urine Formation - Glomerular Filtration Vas afferens, vas efferens • input and output of high-pressure glomerular capillary net glomerular blood flow = P - P 1 v.a. 1 v.e. Rv.a. + Rv.e. + • t resistance of vas aff. or vas eff. -> J, renal blood flow (if the arterial pressure is stable) • control the glomerular filtration pressure: -N constriction of vas aff. -» i glomerular pressure -» i filtration constriction of vas eff. -» t glomerular pressure -» t filtration 'fir/15 Urine Formation - Tubular Processes Peritubular capillary Tubular cells Active Passive (diffusion) Osmosis REABSORPTION FILTRATION Lumen Paracellular path Transcellular path Solutes EXCRETION \ Guyton & Hall. Textbook of Medical Physiology Urine Formation - Tubular Processes Active Transport Mechanisms 1) Primary active transport 2) Secondary active transport 3) Pinocytosis (big molecules, e.g. proteins, namely in the proximal tubule) Urine Formation - Tubular Processes Active Transport Mechanisms 1) Primary active transport Peritubular capillary Tubular epithelial cells -Basal channels Tubular lumen Na+ (-3 mv) ^-Tight junction Brush border (luminal membrane) Interstitial fluid Basement membrane Intercellular space Guyton & Hall. Textbook of Medical Physiology A Urine Formation - Tubular Processes Active Transport Mechanisms 1) Primary active transport - Na+/K+ATPase - H+ATPase - H+/K+ATPase - Ca2+ATPase Urine Formation - Tubular Processes Active Transport Mechanisms 2) Secondary active transport Interstitial fluid Tubular cells Co-transport ----- Glucose *(att} K+ V f> Na+ -70 mV ----Amino acids < j k Glu < > fa Na+ «y i Na+ O ^ Am Tubular lumen Glucose symport Amino acids «y \ Na+ lumen-intersticium , concentration gradient -> H20 osmosis into intersticium 2) Reabsorption of solutes by diffusion ■ CI" (Na+ into intersticium, reabsorption of H20 by osmosis) ■ urea (reabsorption of H20 by osmosis) y Urine Formation - Tubular Processes Peritubular capillary [ Tubular lumen ■Tight junction Brush border (luminal membrane) Interstitial Basement fluid membrane Intercellular space t Lumen negative potential Na+ reabsorption H20 reabsorption t I \ Passive Cl~ reabsorption Luminal CI" concentration t Luminal urea concentration Passive urea reabsorption Guyton & Hall. Textbook of Medical Physiology Urine Formation - Tubular Processes Peritubular capillary Tubular cells Active Passive (diffusion) Osmosis REABSORPTION FILTRATION Lumen Paracellular path Transcellular path Solutes EXCRETION \ Guyton & Hall. Textbook of Medical Physiology Urine Formation - Tubular Processes Physical Forces in Peritubular Capillaries and in Renal Intersticium - tubular reabsorption is controlled by hydrostatic and coloid osmotic forces (similar/ to GFR) GFR= Kf • net filtration pressure I .__ TRR= Kf • net reabsorptive force Urine Formation - Tubular Processes Physical Forces in Peritubular Capillaries and in Renal Intersticium Peritubular Interstitial Tubular Tubular capillary fluid cells lumen Urine Formation - Tubular Processes Tubuloglomerular feedback Glomerulotubular balance Glomerulotubular balance Renal arteriolar pressure Glomerular capillary pressure GFR Solute reabsorption in proximal tubule Solute reabsorption in thick ascending limb Tubuloglomerular feedback Salt and fluid delivery to the distal tubule Ganong's Review of Medical Physiology, 23rd edition Urine Formation - Tubular Processes Proximal Tubule 1) complete reabsorption of substances playing key roles for the organism (glucose, amino acids) 2) partial reabsorption of substances important for the Y organism (ions - Na+, K+, CI", etc.) ^ 65% 3) 4) 5) reabsorption of water secretion of H+ reabsorption of HC03 Result: isoosmotic fluid, notably decreased volume Urine Formation - Tubular Processes Loop of Henle 1) thin descending part - passive reabsorption of water (osmosis) 2) thick ascending part - active reabsorption of ions (Na+/K+/2CI_ symport), secretion of H+, reabsorption of HC03- Result: hypotonic fluid, volume further decreased Urine Formation - Tubular Processes Loop of Henle 1) thin descending part - passive reabsorption of water (osmosis) 2) thick ascending part - active reabsorption of ions (Na+/K+/2CI_ symport), secretion of H+, reabsorption of HC03" Renal interstitial fluid Tubular cells Paracellular diffusion r (atp) K+—V / » Tubular lumen (+8 mV) Na+, K+ « Mg« Ca« -—-CI- TT" i. Loop diuretics • Furosemide • Ethacrynic acid • Bumetanide Urine Formation - Tubular Processes Distal tubule 1) juxtaglomerular apparatus 2) active reabsorption of solutes similar to the thick ascending loop of Henle, also no permeability for urea and water - ^ the so called dilution segment (dilutes the tubular fluid) i Urine Formation - Tubular Processes Collecting duct (+ end of distal tubule) 1) principal cells - reabsorption of Na+ and water (ADH), secretion of K+ Late distal tubule and collecting tubule r Principal cells Intercalated cells Renal interstitial fluid Tubular cells Tubular lumen (-50 mV) Aldosterone antagonists • Spironolactone • Eplerenone Na channel blockers • Amiloride • Triamterene Urine Formation - Tubular Processes Collecting duct (+ end of distal tubule) 1) principal cells - reabsorption of Na+ and water (ADH), secretion of K+ 2) intercalated cells - secretion of H+, reabsorption of HC03" and K+ Urine Formation - Tubular Processes Collecting duct - medullar part 1) reabsorption of Na+ and CI", water (ADH), urea 2) secretion of H+, reabsorption of HC03" Medullary collecting duct Urine Formation - Tubular Processes pronounced secretion in comparison with H20 Proximal tubule Loop of Henle Distal tubule Collecting i tubule pronounced reabsorption in comparison with H20 Guyton & Hall. Textbook of Medical Physiology Examination of renal function Renal clearance Examination of function of renal tubules a) Examination of concentration ability of kidneys - Concentration test using thirstiness (very unpleasant; 12 hours of thirstiness, urine sample every 4 hours - urine density and osmolality; also a blood sample) - Ad iu ret in test (more pleasant for patient; no drinks and food during night, ADH application in the morning through the nasal mucosa -urine density and osmolality) a a) Examination of dilution ability of kidneys (test of reaction on increased water intake - decreased ADH /Ji production + increased diuresis in healthy people) Renal Clearance = the volume of plasma that is cleared of the substance by kidneys per unit time Using clearance, we can quantified the excretion ability of kidneys, the velocity of renal blood flow and even basic functions of kidneys (GFR, tubular reabsorption and secretion) vus vus [ml/min] Renal Clearance Determination of renal plasma flow velocity (RPF) Clearance of a substance that is fully cleared from plasma in glomerulotubular apparatus. PAH (paraaminohippuric acid) cleared by 90% PPAH = 0.01 mg/ml Renal plasma flow RPF = 5.85 x 1 mg/min 0.01 mg/ml = 585 ml/min Renal venous PAH = 0.001 mg/ml UPAH = 5.85 mg/ml V = 1 ml/min Guyton & Hall. Textbook of Medical Physiology Correction to the extraction ratio of PAH (EPAH): 585 ml/min PAH PpAH " VpAH PAH = 0.9 —> RPF = = 650 ml/min 0.9 Renal Clearance Determination of glomerular filtration rate (GFR) Clearance of a substance that is fully filtered in the glomerulus and is not reabsorbed/secreted in tubules. Inulin Creatinine Uinulin=125 m9/ml V = 1 ml/min Guyton & Hall. Textbook of Medical Physiology Renal Clearance Calculation of Filtration Fraction (FF) FF is the fraction of plasma filtered through the glomerular membrane. GFR = 125 ml/min _ _^ -20% of plasma is filtered RPF 650 ml/min in the glomerulus 1 Calculation of Tubular Reabsorption/Secretion A. GFR • Po > V • Uc substance reabsorbed B. GFR • Po < V • Uc substance secreted