Renal Physiology II Tubular functions
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1 Renal Physiology II Tubular functions LO. 42, 43 Dr. Kékesi Gabriella
2 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
3 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
4 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
5 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
6 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
7 Cell subtypes in all segments, and the anatomic differences between them correlate with differences in function.
8 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
9 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
10 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: mmol/l Tm: mol/l Plasma glucose (mmol/l) Reabsorption is saturated Glucose appears in urine Diabetes mellitus
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13 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
14 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)
15 Proximal tubule High water permeability (passive) Osmotic diuresis (iv. mannit, diabetic hyperglycaemia) Polyuria and loose of solutes
16 Osmotic diuresis Polyuria Electrolite deficit
17 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
18 Na + & Cl - reabsorption in the thick ascending limb of loop of Henle Ad interstitium
19
20 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 +
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22 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
23 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
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25 Loop of Henle Zones with different osmolality NaCl, urea and water permeability Countercurrent exchanger Countercurrent multiplier
26 Juxtaglomerularar nephron Vasa recta system
27 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
28
29 Vasa recta counter-current exchanger mechanism H 2 O NaCl, urea H 2 O NaCl, urea H 2 O NaCl, urea 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
30 Counter-current mechanisms
31 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
32 CONCENTRATION AND DILUTION: EFFECTS OF ADH
33
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