L5 Proximal Tubular Reabsorption and Secretion

Question 1

What does the proximal tubule absorb? Percentage of each?

Na+ (_____________________)

Cl- (_____________________)

Glucose (_____________________)

Protein/amino-acids (_____________________)

HCO3 (_____________________)

Water (_____________________)

Answer 1

Na+ (⅔ filtered is reabsorbed)

Cl- (⅔ filtered is reabsorbed)

Glucose (virtually all)

Protein/amino-acids (virtually all)

HCO3 (80% filtered is reabsorbed)

Water (absorbed osmotically along with solutes)

Question 2

________ of all human genes code for transport proteins.

Answer 2

5%-10% of all human genes code for transport proteins.

Question 2

In first half of PCT, Na+ reabsorbed primarily with ____________ and ______________

In second half of PCT, Na+ reabsorbed with ____________ and ________________

Answer 2

In first half, Na+ reabsorbed primarily with Bicarbonate (HCO3-) and Glucose

In second half, Na+ reabsorbed with Cl- and Glucose

Question 3

In the early proximal tubule, there is a _______________________ across the cells created by Na+ cotransporters (bringing net positive charge into the cell and leaving negative charge in the lumen)

Answer 3

In the early proximal tubule, there is a lumen-negative potential difference across the cells created by Na+ cotransporters (bringing net positive charge into the cell and leaving negative charge in the lumen)

Question 4

First Half of PCT
______________ are on the apical membrane and bring in Glucose along Na+ concentration gradient (#?)

_________________ on the basolateral surface allow glucose into the interstitial space

_____________ brings Na+ into the cell and H+ ions from cellular metabolism are secreted in the first half of the PCT

____________ transports bicarbonate from cells of the first half of the PCT into interstitial space

Answer 4

SGLT2 Glucose Symporters are on the apical membrane and bring Glucose along Na+ concentration gradient (1 Na+ w/ 1 Glucose)

Glucose Uniporters (GLUT2) on the basolateral surface allow glucose into the interstitial space

Na+/H+ Antiporter (NHE3) brings Na+ into the cell and H+ ions from cellular metabolism are secreted in the first half of the PCT

Na+/HCO3 Symporter (NBC1) transport bicarbonate from cells of the first half of the PCT into interstitial space

Question 5

Why does the concentration of tubular Cl- along the length of PCT rise?

Answer 5

The concentration of tubular Cl- along the length of PCT RISES due to:

• more water being reabsorbed than Cl
• preferential reabsorption of Na+ with HCO3-in first half of PCT (NO Cl- Transporters)

Question 6

Second half of the PCT

Tubular fluid has little ______ and high ______

____________ on the apical membrane bring Glucose along the Na+ concentration gradient into cells (#?)

_________on the basolateral surface allow glucose into the interstitial space

Answer 6

The second half of PCT Tubular fluid has little Glucose and high Cl-

SGLT1 Glucose Symporters on the apical membrane bring Glucose along Na+ concentration gradient into cells (2 Na+ w/ 1 Glucose)

Glucose Uniporters (GLUT1) on the basolateral surface allow glucose into the interstitial space

Question 7

________________________: Antiporter on apical surface of the proximal tubule that secretes organic ANIONs into the tubule lumen

_______________________: ATPase transporter on the apical surface of the proximal tubule that secretes organic ANIONs into the tubule lumen

Example Anion?

Answer 7

Organic Anion Transporter (OAT4): Antiporter on apical surface of the proximal tubule that secretes organic ANIONa into the tubule lumen

Multidrug resistance-associated protein (MRP2): ATPase transporter on the apical surface of the proximal tubule that secretes organic ANIONs into the tubule lumen

__Example:_: PAH, Urate

Question 8

Antiporters on apical surface of the proximal tubule that secrete organic CATIONs into the tubule lumen?

Answer 8

Multidrug resistance-associated protein (MRP1)- Large cations

Organic cation transporter (OCTN/OCT)- Small cations

Question 9

Organic Cation secretion (PCT)

1. Apical cation transport is fueled by Na+/K+/ATPase pump.
2. Resulting sodium gradient drives H+ out of the cell via the ____________________.
3. Apical OCTN proteins move small cations out of the cell in exchange for H+ while larger cations are transported out via _____________ transporter
4. Cations are transported across basolateral membrane, via passive diffusion or _____________, along concentration gradients.

Example Cation?

Answer 9

1. Apical cation transport is fueled by Na+/K+/ATPase pump.
2. Resulting sodium gradient drives H+ out of the cell by the Sodium Hydrogen Antiporter (NHE3).
3. Apical OCTN proteins move small cations out of the cell in exchange for H+. Larger cations transported out via MDR1 ATPase transporter.
4. Cations are transported across basolateral membrane, via passive diffusion or via OCT 1,2,3, along concentration gradients.

Example: Creatine

Question 10

________________:amount of solute delivered to the tubule per minute that just saturates its transport process

Answer 10

Transfer or Transport Maximum (Tm) ~380mg/min

Question 11

Co-infusion of ________ w/ penicillin (BOTH ____) reduces penicillin excretion extending its biological half-life.

Answer 11

Co-infusion of Hippurates w/ penicillin (BOTH ANIONS) reduces penicillin excretion extending its biological half-life.

Question 12

Why does elevated plasma levels of one cation (or anion) inhibit secretion of the other?

Answer 12

Because organic cations (and anions) compete for the same secretory pathways both reabsorption and secretory transport processes can become saturated i.e. tubular maximum-limited (Tm) systems

Question 13

____________ is particularly critical for the excretion of anions and cations extensively bound to plasma proteins and not filterable at renal corpuscle

Answer 13

PCT secretion is particularly critical for the excretion of anions and cations extensively bound to plasma proteins and not filterable at renal corpuscle

Question 14

How are most proteins reabsorbed from the urine?

Answer 14

Receptor-mediated endocytosis (aka Pinocytosis)

This mechanism reabsorbs virtually all the proteins filtered, and hence the urine is essentially protein free in the healthy kidney

Question 15

What is Splay with regard to Glucose Titration?

Answer 15

Splay of the Excretion curve relative to plasma concentration of glucose is because of nephron heterogeneity; some nephrons can absorb more than others (due to variations in SGLT1 and SGLT2 expression)

Question 16

Renal Threshold vs. Transport Maximum

Answer 16

Renal Threshold = upper limit for reabsorption( [Plasma] ≥ 200mg/dL) => Glucosuria when exceeded

Transport maximum (Tm) for glucose, at which increased
the concentration of Plasma does not result in an increase in the reabsorption of glucose ( ~380mg/min)