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

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”

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

Glucose reabsorption Mechanism of glucose reabsorption Secondary active transport Luminal membrane Cotransport with Na Basolateral membrane GLUT2

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.

Cellular Mechanism for Glucose Reabsorption LUMEN BLOOD Cell of the proximal tubule Na+ Na+ K+ Glucose Glucose Cellular Mechanism for Glucose Reabsorption

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.

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

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.

Glucose Titration Curve UV P Plasma glucose (PG) Inulin Glucose TmG Splay Glucose reabsorbed (TG) “Ideal” Actual Plasma glucose (PG)

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

Tubular maximum (Tmg) Renal threshold 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

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

Glucose filtered, reabsorbed, 800 600 400 200 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)

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.

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

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 +

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

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

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

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

% Proximal tubule length 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

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

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