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. Cellular Mechanism for Glucose Reabsorption
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. 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

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. Glucose Titration Curve UV P Plasma glucose (PG) Inulin Glucose 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) 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

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. 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)
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. % 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
% 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