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TUBULAR REABSORPTION OF GLUCOSE, AMINO ACIDS, UREA & OTHER ELECTROLYTES LECTURE 6.

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Presentation on theme: "TUBULAR REABSORPTION OF GLUCOSE, AMINO ACIDS, UREA & OTHER ELECTROLYTES LECTURE 6."— Presentation transcript:

1 TUBULAR REABSORPTION OF GLUCOSE, AMINO ACIDS, UREA & OTHER ELECTROLYTES LECTURE 6

2 Glucose reabsorption general consideration Glucose reabsorption is calculated as the difference between the amount of glucose filtered by the kidney and the amount excreted.Glucose reabsorption is calculated as the difference between the amount of glucose filtered by the kidney and the amount excreted. When plasma glucose (P G ) is increased to near 200 mg/dl, glucose begins to appear in the urine – this is called the glucose renal thresholdWhen plasma glucose (P G ) is increased to near 200 mg/dl, glucose begins to appear in the urine – this is called the glucose renal threshold

3 As glucose is further increased, more glucose appears in the urine.As glucose is further increased, more glucose appears in the urine. At very high filtered glucose, reabsorption remains constant, this is called tubular transport maximum for glucose (Tm G )At very high filtered glucose, reabsorption remains constant, this is called tubular transport maximum for glucose (Tm G ) –At this maximum transport, all the glucose carriers are saturated and no more glucose can be transported

4 Glucose reabsorption Mechanism of glucose reabsorptionMechanism of glucose reabsorption Secondary active transportSecondary active transport Luminal membraneLuminal membrane –Cotransport with Na Basolateral membraneBasolateral membrane –GLUT2

5 Cellular Mechanism for Glucose Reabsorption The luminal membrane of the epithelial cells faces the tubular fluid (lumen) and contains the Na + -glucose co-transporter. The peritubular membrane or basolateral membrane of the cells faces the peritubular capillary blood and contains the Na + -K + ATPase and the facilitated glucose transporter.

6 Cell of the proximal tubule LUMENBLOOD Na + Glucose Glucose K+K+K+K+ Cellular Mechanism for Glucose Reabsorption

7 Steps involved in reabsorbing glucose from tubular fluid into peritubular capillary blood 1)Glucose move from tubular fluid cell by binding with Na + to the cotransport protein (GLUT1) which rotates in the membrane Na + and glucose released to ICF. Glucose is transported against an electrochemical gradient. 2)Na + gradient is maintained by the Na-K ATPase in the peritubular membrane. Because ATP is used directly to energize the Na-K ATPase and indirectly to maintain the Na gradient, Na + -glucose cotransport called secondary active transport. 3)Glucose transported from cell peritubular capillary blood by facilitated diffusion (GLUT2). Glucose move down electrochemical gradient, no energy required.

8 TUBULARLUMENINTERSTITIALFLUID GLUT 2 SGLT 2 Na + K+K+K+K+ Glucose Glucose One Na + Early proximal tubule cell GLUT 1 SGLT 1 Na + K+K+K+K+ Glucose Glucose Two Na + Late proximal tubule cell Glucose Reabsorption

9 Glucose Titration Curve and T m A glucose titration curve depicts the relationship between plasma glucose concentration and glucose reabsorption. It is best understood by examing each relationship separately and then by considering all three relationships together.

10 Inulin Glucose P UV Plasma glucose (P G ) Glucose reabsorbed (T G ) Tm G Splay IdealActual GlucoseTitrationCurve

11 Renal threshold = 300 mg/dl 375 mg/min (Tm G ) divided by 125 ml/min (GFR) Actual renal threshold = 200 mg/dl

12 Tubular maximum (Tmg)Tubular maximum (Tmg) –Maximum absorptive capacity for glucose by renal tubular cells –375 mg/min (female 300mg/min) Renal thresholdRenal threshold –Plasma glucose level at which glucose first appear in urine –200mg/dl in arterial; 180 mg/dl in venous

13 Glucose absorption is inhibited by Phlorhizin competes for binding to the carrierGlucose absorption is inhibited by Phlorhizin competes for binding to the carrier blood glucose level ( renal threshold) exceed Tm glucose in urine glucosuria Diabetes Mellitus blood glucose level ( renal threshold) exceed Tm glucose in urine glucosuria Diabetes Mellitus

14 Plasma glucose (mg/dl) Glucose filtered, reabsorbed, or excreted (mg/min) Threshold (200) Splay Excreted U G x V Tm G (375) Reabsorbed Filtered GFR x P G

15 The threshold for glucose is affected by the following: GFR – a low GFR causes an increased threshold because the filtered glucose is decreased and the kidney can reabsorb the filtered glucose even though the plasma glucose is increased (more time for reabsorption)GFR – a low GFR causes an increased threshold because the filtered glucose is decreased and the kidney can reabsorb the filtered glucose even though the plasma glucose is increased (more time for reabsorption) Tm G – a decreased Tm G lowers the threshold because the tubules have a reduced capacity to reabsorb glucose.Tm G – a decreased Tm G lowers the threshold because the tubules have a reduced capacity to reabsorb glucose. Splay – rounded as it approaches its maximum which is caused by different nephrons having different reabsorption and filtering capacities.Splay – rounded as it approaches its maximum which is caused by different nephrons having different reabsorption and filtering capacities.

16 Amino acid reabsorption All filtered AAs are reabsorbed in PCTAll filtered AAs are reabsorbed in PCT Luminal membraneLuminal membrane –Cotransport with Na Basolateral membraneBasolateral membrane –diffusion

17 Bicarbonate reabsorption 90% of filtered is reabsorbed in PCT90% of filtered is reabsorbed in PCT Filtered HCO 3 + H 2 O H 2 CO 3Filtered HCO 3 + H 2 O H 2 CO 3 H 2 CO 3 H 2 O + CO 2 in the presence of carbonic anhydraseH 2 CO 3 H 2 O + CO 2 in the presence of carbonic anhydrase CO 2 diffuses into the cell + H 2 O H 2 CO 3CO 2 diffuses into the cell + H 2 O H 2 CO 3 H 2 CO3 CA H + HCO 3H 2 CO3 CA H + HCO 3 HCO 3 is reabsorpedHCO 3 is reabsorped H + is secreted in exchange for Na +H + is secreted in exchange for Na +

18 Bicarbonate reabsorption cont. Lumen Tubular cell Blood Na + Filtrate Na + Na + HCO 3 HCO 3 + H+ H+ H 2 CO 3 H 2 CO 3 H 2 O + CO 2 H 2 CO 3 CA CA CO 2 + H 2 O H+H+H+H+ HCO 3 HCO 3 Tight junction Brush border

19 Phosphate reabsorption Bones, teeth & skeleton (80%)Bones, teeth & skeleton (80%) Intracellular P (20%)Intracellular P (20%) Plasma P 1mmol/l freely filteredPlasma P 1mmol/l freely filtered 1/3 of filtered is excreted in urine1/3 of filtered is excreted in urine Cotransported with NaCotransported with Na Rate of absorption is under the control of PTH & VD ( rate of absorption)Rate of absorption is under the control of PTH & VD ( rate of absorption) Compete with glucose: blocking glucose P reabsorptionCompete with glucose: blocking glucose P reabsorption

20 Urea reabsorption Plasma urea concentraion 15-40mg/100mlPlasma urea concentraion 15-40mg/100ml End product of protein metabolismEnd product of protein metabolism 40-50% of filtered urea reabsorbed40-50% of filtered urea reabsorbed –Passive diffusion –Reabsorbed in consequent of Na reabsorption 50-60% excreted50-60% excreted –GFR –Concentration in blood

21 Urea reabsorption cont. GFR (renal disease; low renal blood flow) urea concentraion in plasma GFR (renal disease; low renal blood flow) urea concentraion in plasma – GFR urea filtered – GFR slow flow rate of filterate more urea is absorbed to blood

22 Inulin Cl Cl K+K+K+K+ Na + osm HCO 3 HCO 3 Aminoacids Glucose % Proximal tubule length TFP

23 Tubular secretion From peritubular blood interstitium tubular cell tubular lumenFrom peritubular blood interstitium tubular cell tubular lumen Secretion:Secretion: –Passive NH3, salicylic acid –Active Tm: creatinine; PAHTm: creatinine; PAH No Tm: K; HNo Tm: K; H

24 Tubular secretion cont. PotassiumPotassium –90% of filtered K is reabsorbed (PCT) –K secreted DCT In exchange for Na; under the control of Aldosterone HydrogenHydrogen –Excretion is inversely proportional to K


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