TUBULAR REABSORPTION OF GLUCOSE, AMINO ACIDS, UREA & OTHER ELECTROLYTES

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. • When plasma glucose (PG) 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. • At very high filtered glucose, reabsorption remains constant, this is called “tubular transport maximum” for glucose (TmG) • At this maximum transport, all the glucose carriers are saturated and no more glucose can be transported

4. Glucose reabsorption • Mechanism of glucose reabsorption • Secondary active transport • Luminal membrane • Cotransport with Na • Basolateral 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. LUMEN BLOOD Cell of the proximal tubule Na+ Na+ K+ Glucose Glucose Cellular Mechanism for Glucose Reabsorption

7. Steps involved in reabsorbing glucose from tubular fluid into peritubular capillary blood • 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. • 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. • Glucose transported from cell  peritubular capillary blood by facilitated diffusion (GLUT2). Glucose move down electrochemical gradient, no energy required.

8. K+ Na+ Glucose Glucose GLUT 2 SGLT 2 One Na+ Early proximal tubule cell Glucose Reabsorption INTERSTITIAL FLUID TUBULAR LUMEN K+ Na+ Glucose Glucose GLUT 1 SGLT 1 Two Na+ Late proximal tubule cell

9. Glucose Titration Curve and Tm 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 Titration Curve UV Glucose P TmG Splay Glucose reabsorbed (TG) “Ideal” Actual Plasma glucose (PG)

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

12. Tubular maximum (Tmg) • Maximum absorptive capacity for glucose by renal tubular cells • 375 mg/min (female 300mg/min) • Renal 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 carrier •  blood glucose level ( renal threshold)  exceed Tm  glucose in urine  glucosuria Diabetes Mellitus

14. 800 600 400 200 0 Filtered GFR x PG Excreted UG x V Glucose filtered, reabsorbed, or excreted (mg/min) TmG (375) Reabsorbed Splay Threshold (200) 0 200 400 600 800 Plasma glucose (mg/dl)

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) • TmG – a decreased TmG 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.

16. Amino acid reabsorption • All filtered AAs are reabsorbed in PCT • Luminal membrane • Cotransport with Na • Basolateral membrane • diffusion

17. Bicarbonate reabsorption • 90% of filtered is reabsorbed in PCT • Filtered HCO3 + H2O H2CO3 • H2CO3 H2O + CO2 in the presence of carbonic anhydrase • CO2 diffuses into the cell + H2OH2CO3 • H2CO3  CA  H + HCO3 • HCO3 is reabsorped • H+ is secreted in exchange for Na +

18. Bicarbonate reabsorption cont. Lumen Tubular cell Blood Filtrate  Na+ HCO3 + H+  H2CO3  H2O + CO2 Na+ H+ HCO3 H2CO3  CA CO2 + H2O Tight junction Brush border

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

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

21. Urea reabsorption cont. • 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. 2.6 2.4 2.2 2.0 1.8 1.6 1.4 1.2 1.0 0.8 0.6 0.4 0.2 Inulin Cl K+ Na+ TF P osm HCO3 Amino acids Glucose 0 25 30 75 100 % Proximal tubule length

23. Tubular secretion • From peritubular blood  interstitium  tubular cell  tubular lumen • Secretion: • Passive NH3, salicylic acid • Active • Tm: creatinine; PAH • No Tm: K; H

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