Tubular reabsorption and secretion

Tubular reabsorption and secretion, including transport processes and proteins: After filtration at the glomerulus, water and electrolytes (Na+, K+, Ca2+, HCO3-) and solutes (glucose, amino acids, etc.) are reabsorbed from the tubular fluid back into the peritubular capillaries. In contrast, organic acids, organic bases, and K+ can be secreted from the peritubular capillaries into the tubular fluid.

Glucose: Two transporters are key for glucose reabsorption:
- The Na±glucose cotransporter (SGLT) on the luminal membrane
- GLUT 1 and GLUT 2 on the basolateral membrane
SGLT moves one molecule of glucose along with two molecules of Na+ into the cell by secondary active transport. The energy for this comes from the Na+ gradient across the cell membrane. That Na+ gradient is maintained by the Na±K+ ATPase pump.

GLUT 1 and GLUT 2 then move glucose from the cell into the circulation by facilitated diffusion, which does not require ATP.
- Below a plasma glucose concentration of 200 mg/dl, all filtered glucose is reabsorbed.
- Above 200 mg/dl, most glucose is still reabsorbed, but some appears in urine because the glucose transporters are approaching saturation.
The plasma concentration at which glucose first appears in urine is called the renal threshold for glucose. As plasma glucose rises above this threshold, more glucose is excreted in urine. At about 350 mg/dl, all carriers are saturated and no additional glucose can be reabsorbed. This level is called Tm (transport maximum).

When you plot glucose excretion and reabsorption against plasma glucose level, you see a splay. Splay is the region of the curve where reabsorption is approaching saturation, and it corresponds to the first appearance of glucose in urine. It can be explained by:
- The low affinity of SGLT for glucose as it approaches Tm
- Differences among nephrons, since each nephron has its own Tm for glucose
The Tm for the kidney as a whole depends on the average Tm of all nephrons.
Urea: Urea is both reabsorbed and secreted by the tubules to some extent.
- About 50% of filtered urea is reabsorbed in the proximal tubule (PCT) by simple diffusion, driven by the urea gradient.
- In the thin descending limb of the loop of Henle, urea is secreted into the lumen.
- The thick ascending limb, distal tubule, and the cortical and outer medullary collecting ducts are normally impermeable to urea.
When ADH is high (e.g., dehydration), a urea transporter called UT1 is activated in the inner medullary collecting ducts. Under these conditions, ADH causes reabsorption of approximately 70% of filtered urea.
Organic acids, bases and PAH: PAH is secreted into the tubules in the proximal tubule by PAH transporters OAT 1 and OAT 3. These act as antiporters. The same transporter also secretes penicillin and is blocked by probenecid.

Weak acids and bases are secreted by the proximal tubule, and their urinary excretion is affected by non-ionic diffusion, which depends on urine pH.
- In acidic urine, weak acids (e.g., aspirin) exist mainly in a unionized form.
- At alkaline pH, weak acids are predominantly in the charged (ionized) form.
Urinary excretion increases when weak acids and bases are in the ionized form. Therefore, aspirin excretion is higher in alkaline urine and lower in acidic urine.

Weak bases (e.g., morphine) behave in the opposite way:
- They are charged at acidic pH.
- They are unionized at alkaline pH.
Urinary excretion of weak bases is increased in acidic urine and decreased in alkaline urine. Based on this principle, alkalinization of urine is used to treat aspirin toxicity.

Glucose: Two transporters are key for glucose reabsorption:
- The Na±glucose cotransporter (SGLT) on the luminal membrane
- GLUT 1 and GLUT 2 on the basolateral membrane
SGLT moves one molecule of glucose along with two molecules of Na+ into the cell by secondary active transport. The energy for this comes from the Na+ gradient across the cell membrane. That Na+ gradient is maintained by the Na±K+ ATPase pump.

GLUT 1 and GLUT 2 then move glucose from the cell into the circulation by facilitated diffusion, which does not require ATP.
- Below a plasma glucose concentration of 200 mg/dl, all filtered glucose is reabsorbed.
- Above 200 mg/dl, most glucose is still reabsorbed, but some appears in urine because the glucose transporters are approaching saturation.
The plasma concentration at which glucose first appears in urine is called the renal threshold for glucose. As plasma glucose rises above this threshold, more glucose is excreted in urine. At about 350 mg/dl, all carriers are saturated and no additional glucose can be reabsorbed. This level is called Tm (transport maximum).

When you plot glucose excretion and reabsorption against plasma glucose level, you see a splay. Splay is the region of the curve where reabsorption is approaching saturation, and it corresponds to the first appearance of glucose in urine. It can be explained by:
- The low affinity of SGLT for glucose as it approaches Tm
- Differences among nephrons, since each nephron has its own Tm for glucose
The Tm for the kidney as a whole depends on the average Tm of all nephrons.
Urea: Urea is both reabsorbed and secreted by the tubules to some extent.
- About 50% of filtered urea is reabsorbed in the proximal tubule (PCT) by simple diffusion, driven by the urea gradient.
- In the thin descending limb of the loop of Henle, urea is secreted into the lumen.
- The thick ascending limb, distal tubule, and the cortical and outer medullary collecting ducts are normally impermeable to urea.
When ADH is high (e.g., dehydration), a urea transporter called UT1 is activated in the inner medullary collecting ducts. Under these conditions, ADH causes reabsorption of approximately 70% of filtered urea.
Organic acids, bases and PAH: PAH is secreted into the tubules in the proximal tubule by PAH transporters OAT 1 and OAT 3. These act as antiporters. The same transporter also secretes penicillin and is blocked by probenecid.

Weak acids and bases are secreted by the proximal tubule, and their urinary excretion is affected by non-ionic diffusion, which depends on urine pH.
- In acidic urine, weak acids (e.g., aspirin) exist mainly in a unionized form.
- At alkaline pH, weak acids are predominantly in the charged (ionized) form.
Urinary excretion increases when weak acids and bases are in the ionized form. Therefore, aspirin excretion is higher in alkaline urine and lower in acidic urine.

Weak bases (e.g., morphine) behave in the opposite way:
- They are charged at acidic pH.
- They are unionized at alkaline pH.
Urinary excretion of weak bases is increased in acidic urine and decreased in alkaline urine. Based on this principle, alkalinization of urine is used to treat aspirin toxicity.