Renal Physiology II Tubular functions LO. 42, 43 Dr. Kékesi Gabriella
Basic points of renal physiology 1. Glomerular filtration (GF) a) Ultrafiltration 2. Tubular functions active and passive a) Reabsorption Removal of water and solutes from the tubular fluid b) Secretion secretion of solutes into the tubular fluid
Afferent arteriole Tubular functions Efferent arteriole Glomerular capillaries Bowman s capsule Tubuli Peritubular capillaries Filtration Reabsorption Secretion Amount excreted Amount Amount = + - filtered secreted Amount reabsorbed
Measurement of tubular function Clearance The volume of plasma that is completely cleared from a particular substance in unit time (ml/min) Its significance: Way of subtsances along the urinary system To determine the funcionality of the kidney Determination of RBF, RPF, GFR
Plasma Clearance The formula used to calculate the clearance of a substance is: C = V x U/P C = plasma clearance rate in ml/min V = urine production rate in ml/min U = the concentration of a substance in the urine in mg/ml P = the concentration of a substance in the plasma in mg/ml
ad. 1 ad. 2 ad. 3 How does the clearance (C) characterize a substance? if C= GFR=120 ml/min pl. inulin if C<GFR no filtered pl. large proteins (C=0 ml/min) filtered, and actively reabsorbed pl. glucose filtered, and passively reabsorbed pl. urea if C>GFR ei. PAH C(PAH)=RPF=660 ml/min
Cell subtypes in all segments, and the anatomic differences between them correlate with differences in function.
Proximal tubule I. solutes Lumen of tubule Na + -H + exchanger Interstitium Na + -K + pump 3 Na + ATPáz 2 K + Na + H + H + + HCO3- H 2 CO 3 H 2 O + CO 2 H + + OH - + CO 2 H 2 O HCO 3 - Na + 3 HCO 3 - K + channel cotransporter H 2 O, Cl - acid Cl - anion H + Na + K + Cl - Cl - channel cotransporter dissociation
Proximal tubule II. Glucose reabsorption sodium-glucose cotransport at the luminar membrane GLUT facilitative transporter toward the interstitium glucosuria Aminoacid reabsorption Sodium-aminoacid cotransporters with different specificity Aminoaciduria Phosphate reabsorption PTH (parathyroid hormone) regulated sodium-phosphate cotransport Reduced phosphate reabsorption Urea (protein metabolism) reabsorption passive diffusion Albumin endocytosis - albuminuria
TUBULAR MAXIMUM (Tm) OF GLUCOSE Tm: maximum amount of glucose that can be transported per minute. Threshold: glucose appears in urine below Tm. The threshold is the glucose loading where the tubule with the lowest threshold is saturated. Filtered, Reabsorbed or Excreted glucose (mmol/min) 3 Splay Normal plasma glucose: 5 mmol/l 2 1 Tm REABSORBED Plasma glucose at: Threshold: 11-13 mmol/l Tm: 22-25 mol/l 0 5 10 15 20 25 30 35 Plasma glucose (mmol/l) Reabsorption is saturated Glucose appears in urine Diabetes mellitus
Parathyroid hormone (PTH) - kidney Decrease phosphate reabsorption - inactivation of a sodium-phosphate cotransporter in the proximal convoluted tubule Increase calcium reabsorption - in the distal tubule acts on a sodiumcalcium co-transporter (5-10%) Stimulate activation of vitamin D - it activates 1 hydroxylase
Proximal tubule III. - secretion Driving force: Na-K pump generated Na + -gradient Low specificity Cationsecretion (ei. creatinine, morphine, atropine) Organic cation/h + exchager at the luminal side Anionsecretion (ei. urate nucleicacid degradation, penicillin, PAH, oxalate, salicylate)
Proximal tubule High water permeability (passive) Osmotic diuresis (iv. mannit, diabetic hyperglycaemia) Polyuria and loose of solutes
Osmotic diuresis Polyuria Electrolite deficit
Loop of Henle Thin descending limb of loop of Henle high permeable cells Passive transports Permeable to water!!! Thin ascending limb of loop of Henle (15%) Thick ascending limb of loop of Henle Active transports: Na + -K + -2Cl - -cotransport inhibitors: furosemide, bumetamide Impermeable to water!!!: no water channels, tight junctions between epithelial cells diluting segment Osmotic gradient inside the kidney
Na + & Cl - reabsorption in the thick ascending limb of loop of Henle Ad interstitium
Distal & connecting tubule Tiazide diuretics Lumen Interstitium 3 Na + Na + -K + pump ATPáz 2 K + Na + Cl - K + conductive K + ch. K + Cl - K + -Cl - cotransporter Ca ++ Na + -K + pump 3 Na + ATPáz 2 K + Ca ++ channel Ca ++ -binding protein Sensitive to calcitriol Binding protein (calbindin) Ca ++ Ca ++ ATPáz Ca ++ pump Na + -Ca ++ exhanger sec. active trp. 3 Na +
Collecting duct Subsegments Cell types Principal and intercalated cells (α és β sejtek) Regulation of the volume of the urine ADH (diabetes insipidus renal/extrarenal) Set the ph of the urine Intercalated cells Regulation of the osmotic concentration
Principal cells K + secretion depends on Na + reabsorption Amiloride-sensitive aldosterone ANP Intercalated cells Regulation of ph of the urine α H + secretion toward the lumen Na + 3 Na + Na + -K + pump ATPáz 2 K + H + pumpa H + ATPáz Cl - H + + OH - + CO H 2 O 2 K + conductive K + ch. K + H + ATPáz HCO - 3 Cl - Cl - K + β H + secretion toward interstitium, HCO 3- secretion toward the lumen aquaporin 2 aquaporin 3 H + ATPáz UTP 1 UTP 2/3 HCO 3 - Cl - Cl - ADH Tubule interstitium Tubule interstitium
Loop of Henle Zones with different osmolality NaCl, urea and water permeability Countercurrent exchanger Countercurrent multiplier
Juxtaglomerularar nephron Vasa recta system
Counter-current multiplier mechanism Descending limb of loop of Henle permeable to water NaCl reabsorption is not followed by water in the thick ascending limb of loop of Henle NaCl concentration in the interstitium increasing
Vasa recta counter-current exchanger mechanism 300 600 900 H 2 O NaCl, urea H 2 O NaCl, urea H 2 O NaCl, urea 300 600 900 1200 Inhibits the wash out of the osmotic gradient from the intersitium Passive Aquaporin 1 water channel, urea transporters Effectivity depends on the flow rate 1200
Counter-current mechanisms
Osmotic concentration of the urine - ADH 10 L/day Diuresis 70 mosm/l AVP level Dilute urine with high urea content 0.5 L/day Antidiuresis 1200 mosm/l V 2 receptor - AC - camp - aquaporin-2 water channel recycling AVP level Concentrated urine with low urea content
CONCENTRATION AND DILUTION: EFFECTS OF ADH