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Glucose Reabsorption & Titration Curve
Reabsorption
  • Sodium-potassium ATPase extrudes sodium from the cell in exchange for potassium.
– This exchange creates the electrochemical gradient that drives the SGLT co-transportation of sodium and glucose into the cell.
  • As sodium moves down its concentration gradient, glucose moves against its concentration gradient.
  • From here, GLUT transporters facilitate glucose diffusion out of the cell to return it to the blood (again, there are multiple types of GLUT transporters, but here we'll simply generalize).
– Within the healthy physiological glucose range, these transporters can completely reabsorb glucose from the proximal tubule; however, as we'll see, at higher plasma concentrations, the transporters are overwhelmed, glucose is incompletely reabsorbed, and thus is excreted in the urine.

Glucose Reabsorption & Titration Curve

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Glucose Reabsorption & Titration Curve
  • Typical plasma glucose concentration is between 70-100 milligrams/deciliters.
Glucose is completely* reabsorbed from the proximal tubule via secondary active transport mechanisms as long as plasma glucose concentrations do not exceed this concentration.
Reabsorption
  • Sodium-potassium ATPase extrudes sodium from the cell in exchange for potassium.
– This exchange creates the electrochemical gradient that drives the SGLT co-transportation of sodium and glucose into the cell.
  • As sodium moves down its concentration gradient, glucose moves against its concentration gradient.
  • From here, GLUT transporters facilitate glucose diffusion out of the cell to return it to the blood (again, there are multiple types of GLUT transporters, but here we'll simply generalize).
– Within the healthy physiological glucose range, these transporters can completely reabsorb glucose from the proximal tubule; however, as we'll see, at higher plasma concentrations, the transporters are overwhelmed, glucose is incompletely reabsorbed, and thus is excreted in the urine.
Glucose Titration Curve
Explains relationships between glucose plasma concentration, reabsorption, and excretion. Filtered load of glucose increases in proportion to plasma glucose levels; this makes sense, because we know that glucose is freely filtered within the renal corpuscle.* (A)
  • Glucose reabsorption follows filtration until plasma glucose concentration reaches approximately 200 milligrams per deciliter. (B)
– At that point, the glucose reabsorption curve begins to bend because glucose transporters are approaching saturation.
  • At plasma glucose concentrations above 350 milligrams per deciliter, glucose reabsorption plateaus as the transporters reach full saturation. (D)
Glucose excretion remains near zero* until glucose plasma concentration rises above 200 milligrams per deciliter (C) – Once this threshold is surpassed, glucose begins to appear in the urine (aka, glucosuria).
  • Then, when plasma glucose concentration rises above of 350-400 milligrams per deciliter, excretion rises in parallel with filtered load. (E)
Summary of some key points in the glucose titration curve.
Filtered load increases in proportion* to plasma glucose concentrations (even when outside of the typical physiological range). Reabsorption matches filtered load* when plasma glucose concentrations remain below 200 milligrams per deciliter.
  • Above this threshold, glucose begins to appear in the urine (aka, glucosuria).
Once plasma glucose concentration rises above 350 milligrams per deciliter, all glucose transporters are saturated*. Transport maximum (Tm) is reached, and glucose reabsorption plateaus*.
  • Once transport maximum is reached, excretion rate rises linearly with filtered load.
Because of a phenomenon called splay, threshold occurs before Tm because of variation* in the transport maximum of individual nephrons due to differences in transport number and types.
Clinical causes of glucosuria.
  • Glucosuria occurs when the filtered load of glucose exceeds the resorptive capabilities, and glucose is excreted in the urine.
  • Diabetes mellitus, the body's inability to make and/or use insulin results in excessive plasma glucose concentrations, which increases its filtered load.
  • Some women experience pregnancy-related glucosuria when increased GFR increases filtered load. This is often benign, and is not synonymous with gestational diabetes.

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